Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders
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The KRAS gene is the most common locus for somatic gain-of-function mutations in human cancer. Germline KRAS mutations were shown recently to be associated with developmental disorders, including Noonan syndrome (NS), cardio-facio-cutaneous syndrome (CFCS), and Costello syndrome (CS). The molecular basis of this broad phenotypic variability has in part remained elusive so far. Here, we comprehensively analyzed the biochemical and structural features of ten germline KRAS mutations using physical and cellular biochemistry. According to their distinct biochemical and structural alterations, the mutants can be grouped into five distinct classes, four of which markedly differ from RAS oncoproteins. Investigated functional alterations comprise the enhancement of intrinsic and guanine nucleotide exchange factor (GEF) catalyzed nucleotide exchange, which is alternatively accompanied by an impaired GTPase-activating protein (GAP) stimulated GTP hydrolysis, an overall loss of functional properties, and a deficiency in effector interaction. In conclusion, our data underscore the important role of RAS in the pathogenesis of the group of related disorders including NS, CFCS, and CS, and provide clues to the high phenotypic variability of patients with germline KRAS mutations.
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RAS mutants were once thought to be locked in the GTP-bound on state and undruggable, but detailed structural and biochemical analyses have revealed differences among RAS mutants in GTPase activity, GDP-GTP exchange and effector binding.
“RAS mutants were once viewed as being ‘locked’ in the GTP-bound ‘on’ state, impervious to GAP-stimulated or intrinsic GTP hydrolysis, and hence undruggable. However, detailed structural and biochemical analyses of various RAS mutants associated with cancer and ‘RASopathies’”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [49]
Some oncogenic KRAS mutants, notably KRASG12C and to a lesser extent KRASG12D, retain significant intrinsic GTPase activity.
“Some oncogenic mutants, notably KRASG12C (G12C) and, to a lesser extent, KRASG12D (G12D), retain significant intrinsic GTPase activity.”
From SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling (2021) · cites this paper as Gremer et al., 2011
V14I displays similar affinity to RAF1 as does the G12V mutant.
“it displays similar affinity to RAF1, as does also the G12V mutant [60].”
The V14I mutation does not change the GTPase activity of KRAS.
“Whereas the V14I mutation does not change the GTPase activity of KRAS”
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Cites
CHARMM: A program for macromolecular energy, minimization, and dynamics calculations
Brooks, B., Bruccoleri, R., Olafson, B. D., States, D., Swaminathan, S., & Karplus, M. (1983) · Journal of Computational Chemistry · doi:10.1002/jcc.540040211 · Cited by 13,736 · see citing works
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061 · see citing works
GEFs and GAPs: Critical Elements in the Control of Small G Proteins
Bos, J. L., Rehmann, H., & Wittinghofer, A. (2007) · Cell · doi:10.1016/j.cell.2007.05.018 · Cited by 1,903 · see citing works
Self-citationRAS oncogenes: the first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1097 · Cited by 1,902 · see citing works
The Guanine Nucleotide-Binding Switch in Three Dimensions
Vetter, I. R., & Wittinghofer, A. (2001) · Science · doi:10.1126/science.1062023 · Cited by 1,875 · see citing works
Self-citationHyperactive Ras in developmental disorders and cancer
Schubbert, S., Shannon, K., & Bollag, G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2109 · Cited by 1,583 · see citing works
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants
Scheffzek, K., Ahmadian, M. R., Kabsch, W., Wiesmüller, L., Lautwein, A., Schmitz, F., & Wittinghofer, A. (1997) · Science · doi:10.1126/science.277.5324.333 · Cited by 1,543 · see citing works
Self-citationRas oncogenes: split personalities
Karnoub, A. E., & Weinberg, R. A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2438 · Cited by 1,467 · see citing works
PAI, E. F., Krengel, U., Petsko, G. A., Goody, R. S., Kabsch, W., & Wittinghofer, A. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07409.x · Cited by 1,074 · see citing works
Self-citationG PROTEIN MECHANISMS: Insights from Structural Analysis
Sprang, S. R. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.639 · Cited by 1,066 · see citing works
Milburn, M. V., Tong, L., deVos, A. M., Brünger, A. T., Yamaizumi, Z., Nishimura, S., & Kim, S. (1990) · Science · doi:10.1126/science.2406906 · Cited by 1,062 · see citing works
The structural basis of the activation of Ras by Sos
Boriack-Sjodin, P. A., Margarit, S. M., Bar-Sagi, D., & Kuriyan, J. (1998) · Nature · doi:10.1038/28548 · Cited by 799 · see citing works
The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation
Tidyman, W. E., & Rauen, K. A. (2009) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2009.04.001 · Cited by 780 · see citing works
Germline KRAS mutations cause Noonan syndrome
Schubbert, S., Zenker, M., Rowe, S. L., Böll, S., Klein, C., Bollag, G., van der Burgt, I., Musante, L., Kalscheuer, V., Wehner, L.-E., et al. (2006) · Nature Genetics · doi:10.1038/ng1748 · Cited by 730 · see citing works
Self-citationNassar, N. N., Horn, G., Herrmann, C., Scherer, A., McCormick, F. P., & Wittinghofer, A. (1995) · Nature · doi:10.1038/375554a0 · Cited by 631 · see citing works
Self-citationCrystal Structure and Functional Analysis of Ras Binding to Its Effector Phosphoinositide 3-Kinase γ
Pacold, M. E., Suire, S., Perišić, O., Lara‐González, S., Davis, C. T., Walker, E. H., Hawkins, P. T., Stephens, L., Eccleston, J. F., & Williams, R. L. (2000) · Cell · doi:10.1016/s0092-8674(00)00196-3 · Cited by 603 · see citing works
Germline KRAS and BRAF mutations in cardio-facio-cutaneous syndrome
Niihori, T., Aoki, Y., Narumi, Y., Neri, G., Cavé, H., Verloès, A., Okamoto, N., Hennekam, R. C. M., Gillessen‐Kaesbach, G., Wieczorek, D., et al. (2006) · Nature Genetics · doi:10.1038/ng1749 · Cited by 599 · see citing works
Biological properties of human c-Ha-ras1 genes mutated at codon 12
Seeburg, P. H., Colby, W. W., Capon, D. J., Goeddel, D. V., & Levinson, A. D. (1984) · Nature · doi:10.1038/312071a0 · Cited by 567 · see citing works
Biological and biochemical properties of human rasH genes mutated at codon 61
Der, C. J., Finkel, T., & Cooper, G. M. (1986) · Cell · doi:10.1016/0092-8674(86)90495-2 · Cited by 547 · see citing works
Margarit, S. M., Sondermann, H., Hall, B. E., Nagar, B., Hoelz, A., Pirruccello, M., Bar‐Sagi, D., & Kuriyan, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00149-1 · Cited by 486 · see citing works
Krengel, U., Schlichting, I., Scherer, A., Schumann, R., Frech, M., John, J., Kabsch, W., Pai, E., & Wittinghofer, A. (1994) · Cell · doi:10.1016/0092-8674(90)90018-a · Cited by 374 · see citing works
Self-citationThe RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders
Aoki, Y., Niihori, T., Narumi, Y., Kure, S., & Matsubara, Y. (2008) · Human Mutation · doi:10.1002/humu.20748 · Cited by 360 · see citing works
Herrmann, C., Martin, G. A., & Wittinghofer, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.7.2901 · Cited by 351 · see citing works
Self-citationDynamic properties of the Ras switch I region and its importance for binding to effectors
Spoerner, M., Herrmann, C., Vetter, I. R., Kalbitzer, H. R., & Wittinghofer, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081441398 · Cited by 324 · see citing works
Self-citationStructural Analysis of Autoinhibition in the Ras Activator Son of Sevenless
Sondermann, H., Soisson, S. M., Boykevisch, S., Yang, S., Bar‐Sagi, D., & Kuriyan, J. (2004) · Cell · doi:10.1016/j.cell.2004.10.005 · Cited by 315 · see citing works
A restricted spectrum of NRAS mutations causes Noonan syndrome
Cirstea, I. C., Kutsche, K., Dvorský, R., Gremer, L., Carta, C., Horn, D., Roberts, A. E., Lepri, F. R., Merbitz-Zahradnik, T., König, R., et al. (2009) · Nature Genetics · doi:10.1038/ng.497 · Cited by 315 · see citing works
Self-citationExpression of p21 proteins in Escherichia coli and stereochemistry of the nucleotide‐binding site.
Tucker, J., Sczakiel, G., Feuerstein, J., John, J., Goody, R. S., & Wittinghofer, A. (1986) · The EMBO Journal · doi:10.1002/j.1460-2075.1986.tb04366.x · Cited by 285 · see citing works
Self-citationKraulis, P. J., Domaille, P. J., Campbell, S. L., Aken, T. V., & Laue, E. D. (1994) · Biochemistry · doi:10.1021/bi00178a008 · Cited by 267 · see citing works
Tong, L., de Vos, A. M., Milburn, M. V., & Kim, S. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90753-s · Cited by 261 · see citing works
Nava, C., Hanna, N., Michot, C., Pereira, S., Pouvreau, N., Niihori, T., Aoki, Y., Matsubara, Y., Arveiler, B., Lacombe, D., et al. (2007) · Journal of Medical Genetics · doi:10.1136/jmg.2007.050450 · Cited by 256 · see citing works
The KRAS oncogene: Past, present, and future
Kranenburg, O. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.10.001 · Cited by 252 · see citing works
Structural basis for the interaction of Ras with RaIGDS
Huang, L., Hofer, F., Martin, G. S., & Kim, S. (1998) · Nature Structural Biology · doi:10.1038/nsb0698-422 · Cited by 248 · see citing works
ras oncogenes: their role in neoplasia
Barbacid, M. (1990) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1990.tb01848.x · Cited by 242 · see citing works
Xu, J., Baase, W. A., Baldwin, E. P., & Matthews, B. W. (1998) · Protein Science · doi:10.1002/pro.5560070117 · Cited by 229 · see citing works
Lenzen, C. U., Cool, R. H., Prinz, H., Kuhlmann, J., & Wittinghofer, A. (1998) · Biochemistry · doi:10.1021/bi972621j · Cited by 227 · see citing works
Self-citationCarta, C., Pantaleoni, F., Bocchinfuso, G., Stella, L., Vasta, I., Sárközy, A., Digilio, C., Palleschi, A., Pizzuti, A., Grammatico, P., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/504394 · Cited by 225 · see citing works
The ribonuclease III site flanking 23S sequences in the 30S ribosomal precursor RNA of E. coli
Bram, R. J., Young, R. A., & STEITZ, J. A. (1980) · Cell · doi:10.1016/0092-8674(80)90513-9 · Cited by 208 · see citing works
Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations
Zenker, M., Lehmann, K., Schulz, A., Barth, H., Hansmann, D., Koenig, R., Korinthenberg, R., Kreiß‐Nachtsheim, M., Meinecke, P., Morlot, S., et al. (2006) · Journal of Medical Genetics · doi:10.1136/jmg.2006.046300 · Cited by 202 · see citing works
Self-citationA novel switch region regulates H‐ras membrane orientation and signal output
Abankwa, D., Hanzal‐Bayer, M., Ariotti, N., Plowman, S. J., Gorfe, A. A., Parton, R. G., McCammon, J. A., & Hancock, J. F. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.10 · Cited by 199 · see citing works
Gelb, B. D., & Tartaglia, M. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl197 · Cited by 197 · see citing works
HRAS mutation analysis in Costello syndrome: Genotype and phenotype correlation
Gripp, K. W., Lin, A. E., Stabley, D. L., Nicholson, L., Scott, C. I., Doyle, D., Aoki, Y., Matsubara, Y., Zackai, E. H., Lapunzina, P. D., et al. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31047 · Cited by 190 · see citing works
Scheidig, A. J., Burmester, C., & Goody, R. S. (1999) · Structure · doi:10.1016/s0969-2126(00)80021-0 · Cited by 187 · see citing works
Estep, A. L., Tidyman, W. E., Teitell, M. A., Cotter, P. D., & Rauen, K. A. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31078 · Cited by 180 · see citing works
Ras–effector interactions: after one decade
Herrmann, C. (2003) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(02)00007-6 · Cited by 179 · see citing works
The structural basis for the transition from Ras-GTP to Ras-GDP
Hall, B. E., Bar‐Sagi, D., & Nassar, N. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192453199 · Cited by 164 · see citing works
Regional Polysterism in the GTP-Bound Form of the Human c-Ha-Ras Protein,
Ito, Y., Yamasaki, K., Iwahara, J., Terada, T., Kamiya, A., Shirouzu, M., Muto, Y., Kawai, G., Yokoyama, S., Laue, E. D., et al. (1997) · Biochemistry · doi:10.1021/bi970296u · Cited by 163 · see citing works
GTPase activating proteins: structural and functional insights 18 years after discovery
Scheffzek, K., & Ahmadian, M. R. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5136-x · Cited by 154 · see citing works
Self-citationTanaka, T. U., Williams, R. L., & Rabbitts, T. H. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601744 · Cited by 151 · see citing works
Guanosine triphosphatase stimulation of oncogenic Ras mutants
Ahmadian, M. R., Zor, T., Vogt, D., Kabsch, W., Selinger, Z., Wittinghofer, A., & Scheffzek, K. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.7065 · Cited by 145 · see citing works
Self-citationAhmadian, M. R., Hoffmann, U., Goody, R. S., & Wittinghofer, A. (1997) · Biochemistry · doi:10.1021/bi962556y · Cited by 141 · see citing works
Self-citationStructural and Mechanistic Insights into Ras Association Domains of Phospholipase C Epsilon
Bunney, T. D., Harris, R., Gandarillas, N. L., Josephs, M. B., Roe, S. M., Sorli, S., Paterson, H. F., Rodrigues‐Lima, F., Esposito, D., Ponting, C. P., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.008 · Cited by 134 · see citing works
Probing the Structure and Mechanism of Ras Protein with an Expanded Genetic Code
Chung, H., Benson, D. R., & Schultz, P. G. (1993) · Science · doi:10.1126/science.8430333 · Cited by 129 · see citing works
Selenomethionine incorporation into a protein by cell-free synthesis
Kigawa, T., Yamaguchi-Nunokawa, E., Kodama, K., Matsuda, T., Yabuki, T., Matsuda, N., Ishitani, R., Nureki, O., & Yokoyama, S. (2002) · Journal of Structural and Functional Genomics · doi:10.1023/a:1013203532303 · Cited by 119 · see citing works
Buhrman, G., Wink, G., & Mattos, C. (2007) · Structure · doi:10.1016/j.str.2007.10.011 · Cited by 116 · see citing works
Isoform-Specific Ras Functions in Development and Cancer
Quinlan, M. P., & Settleman, J. E. (2009) · Future Oncology · doi:10.2217/14796694.5.1.105 · Cited by 111 · see citing works
Reinstein, J., Schlichting, I., Frech, M. S., Goody, R. S., & Wittinghofer, A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47428-0 · Cited by 104 · see citing works
Self-citationStructural and biochemical analysis of Ras‐effector signaling via RalGDS
Vetter, I. R., Linnemann, T., Wohlgemuth, S., Geyer, M., Kalbitzer, H. R., Herrmann, C., & Wittinghofer, A. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00555-4 · Cited by 103 · see citing works
Self-citationBiochemical and Functional Characterization of Germ Line KRAS Mutations
Schubbert, S., Bollag, G. E., Lyubynska, N., Nguyen, H. T., Kratz, C. P., Zenker, M., Niemeyer, C. M., Molven, A., & Shannon, K. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00965-07 · Cited by 99 · see citing works
Self-citationStieglitz, B., Bee, C., Schwarz, D. F., Yıldız, Ö., Moshnikova, A., Khokhlatchev, A. V., & Herrmann, C. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.125 · Cited by 98 · see citing works
Franken, S. M., Scheidig, A. J., Krengel, U., Rensland, H., Lautwein, A., Geyer, M., Scheffzek, K., Goody, R. S., & Kalbitzer, H. R. (1993) · Biochemistry · doi:10.1021/bi00084a005 · Cited by 91 · see citing works
Structure of the G60A Mutant of Ras
Ford, B. A., Skowronek, K., Boykevisch, S., Bar‐Sagi, D., & Nassar, N. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502240200 · Cited by 74 · see citing works
Scheidig, A. J., Franken, S. M., Corrie, J. E. T., Reid, G. P., Wittinghofer, A., PAI, E. F., & Goody, R. S. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0541 · Cited by 67 · see citing works
Self-citationPaternal bias in parental origin ofHRASmutations in Costello syndrome
Sol‐Church, K., Stabley, D. L., Nicholson, L., Gonzalez, I. L., & Gripp, K. W. (2006) · Human Mutation · doi:10.1002/humu.20381 · Cited by 65 · see citing works
Guanine Nucleotide Exchange Factors Operate by a Simple Allosteric Competitive Mechanism
Guo, Z., Ahmadian, M. R., & Goody, R. S. (2005) · Biochemistry · doi:10.1021/bi0518601 · Cited by 62 · see citing works
Self-citationThe role of the metal ion in the p21ras catalysed GTP-hydrolysis: Mn2+ versus Mg2+
Schweins, T., Scheffzek, K., Aßheuer, R., & Wittinghofer, A. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0814 · Cited by 62 · see citing works
Self-citationScheffzek, K., Grünewald, P., Wohlgemuth, S., Kabsch, W., Tu, H., Wigler, M., Wittinghofer, A., & Herrmann, C. (2001) · Structure · doi:10.1016/s0969-2126(01)00674-8 · Cited by 60 · see citing works
Self-citationAn unexpected new role of mutant Ras: perturbation of human embryonic development
Kratz, C. P., Niemeyer, C. M., & Zenker, M. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0135-4 · Cited by 57 · see citing works
Self-citationFluoride complexes of oncogenic Ras mutants to study the Ras-RasGAP interaction
Gremer, L., Gilsbach, B. K., Ahmadian, M. R., & Wittinghofer, A. (2008) · Biological Chemistry · doi:10.1515/bc.2008.132 · Cited by 56 · see citing works
Self-citationFluorescence Methods in the Study of Small GTP-Binding Proteins
Ahmadian, M. R., Wittinghofer, A., & Herrmann, C. (2003) · Humana Press eBooks · doi:10.1385/1-59259-281-3:045 · Cited by 52 · see citing works
Self-citationStructure of a Transient Intermediate for GTP Hydrolysis by Ras
Ford, B. A., Horn̆ák, V., Kleinman, H., & Nassar, N. N. (2006) · Structure · doi:10.1016/j.str.2005.12.010 · Cited by 52 · see citing works
p190-RhoGAP as an integral component of the Tiam1/Rac1-induced downregulation of Rho
Herbrand, U., & Ahmadian, M. R. (2006) · Biological Chemistry · doi:10.1515/bc.2006.041 · Cited by 51 · see citing works
Self-citationDenayer, E., Parret, A. H. A., Chmara, M., Schubbert, S., Vogels, A., Devriendt, K., Frijns, J., Rybin, V., de Ravel, T. J. L., Shannon, K., et al. (2007) · Human Mutation · doi:10.1002/humu.20616 · Cited by 49 · see citing works
Hemsath, L., & Ahmadian, M. R. (2005) · Methods · doi:10.1016/j.ymeth.2005.05.014 · Cited by 47 · see citing works
Self-citationGremer, L., Luca, A. D., Merbitz-Zahradnik, T., Dallapiccola, B., Morlot, S., Tartaglia, M., Kutsche, K., Ahmadian, M. R., & Rosenberger, G. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp548 · Cited by 43 · see citing works
Self-citationA Novel Activating Mutation of the K-ras Gene in Human Primary Colon Adenocarcinoma
Tsukuda, K., Tanino, M., Soga, H., Shimizu, N., & Shimizu, K. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3839 · Cited by 42 · see citing works
Organic Solvents Order the Dynamic Switch II in Ras Crystals
Buhrman, G., de Serrano, V. S., & Mattos, C. (2003) · Structure · doi:10.1016/s0969-2126(03)00128-x · Cited by 42 · see citing works
Quilliam, L. A., Zhong, S., Rabun, K. M., Carpenter, J. W., South, T. L., Der, C. J., & Campbell, S. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.5.1272 · Cited by 41 · see citing works
Lo, F., Lin, J., Kuo, M.-T., Chiu, P., Shu, S., Chao, M., Lee, Y., & Lin, S. (2008) · European Journal of Pediatrics · doi:10.1007/s00431-008-0858-z · Cited by 36 · see citing works
Monitoring the real-time kinetics of the hydrolysis reaction of guanine nucleotide-binding proteins
Eberth, A., Dvorský, R., Becker, C. F. W., Beste, A., Goody, R. S., & Ahmadian, M. R. (2005) · Biological Chemistry · doi:10.1515/bc.2005.127 · Cited by 33 · see citing works
Self-citationHwang, M.-C. C., Sung, Y., & Hwang, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.14.8196 · Cited by 32 · see citing works
Klink, B. U., Goody, R. S., & Scheidig, A. J. (2006) · Biophysical Journal · doi:10.1529/biophysj.105.078931 · Cited by 30 · see citing works
Gasper, R., Thomas, C., Ahmadian, M. R., & Wittinghofer, A. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.03.011 · Cited by 27 · see citing works
Self-citationStone, J. C., Colleton, M., & Bottorff, D. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.12.7311-7320.1993 · Cited by 27 · see citing works
Ahmadian, M. R. (2002) · British Journal of Haematology · doi:10.1046/j.0007-1048.2001.03314.x · Cited by 26 · see citing works
Self-citationRidley, A. J., & Frampton, J. (2003) · Medical Entomology and Zoology · Cited by 22 · see citing works
A novel activating mutation of the K-ras gene in human primary colon adenocarcinoma
佃, 和. (2001) · Institutional Repositories DataBase (IRDB) · doi:10.11501/3182404 · Cited by 22 · see citing works
Der, C. J. (1989) · Cancer treatment and research · doi:10.1007/978-1-4613-1599-5_4 · Cited by 20 · see citing works
Scheidig, A. J., Sanchez-Llorente, A., Lautwein, A., PAI, E. F., Corrie, J. E. T., Reid, G. P., Wittinghofer, A., & Goody, R. S. (1994) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744499301443x · Cited by 20 · see citing works
Self-citationCorrection: RAS oncogenes: The first 30 years
Malumbres, M., & Barbacid, M. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1193 · Cited by 19 · see citing works
The Dominant Negative Effects of H-Ras Harboring a Gly to Ala Mutation at Position 60
Sung, Y., Hwang, M.-C. C., & Hwang, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.48.30537 · Cited by 18 · see citing works
Pechlivanis, M., Ringel, R., Popkirova, B., & Kuhlmann, J. (2007) · Biochemistry · doi:10.1021/bi602353k · Cited by 17 · see citing works
Effect of phospholipid on conformation of ovine luteinizing hormone as tested by circular dichroism
Ward, D. N., & Jirgensons, B. (1974) · FEBS Letters · doi:10.1016/0014-5793(74)80839-2 · Cited by 7 · see citing works
Paleopathology of malignant tumours supports the concept of human vulnerability to cancer
Nerlich, M. L., & Bachmeier, B. E. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2071-c1 · Cited by 5 · see citing works
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- Krengel U Struktur und Guanosintriphosphathydrolysemechanismus des C-terminal verkürzten menschlichen Krebsproteins P21-H-RAS Ph.D. thesis 1991 Heidelberg
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Ras in Cancer and Developmental Diseases
Fernández‐Medarde, A., & Santos, E. (2011) · Genes & Cancer · doi:10.1177/1947601911411084 · Cited by 959 · see citing works
Roberts, A. E., Allanson, J. E., Tartaglia, M., & Gelb, B. D. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61023-x · Cited by 791 · see citing works
The current state of the art and future trends in RAS-targeted cancer therapies
Punekar, S. R., Velcheti, V., Neel, B. G., & Wong, K.-K. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00671-9 · Cited by 549 · see citing works
KRAS Alleles: The Devil Is in the Detail
Haigis, K. M. (2017) · Trends in Cancer · doi:10.1016/j.trecan.2017.08.006 · Cited by 373 · see citing works
Portrait of the PI3K/AKT pathway in colorectal cancer
Danielsen, S. A., Eide, P. W., Nesbakken, A., Guren, T. K., Leithe, E., & Lothe, R. A. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.09.008 · Cited by 326 · see citing works
Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia
Li, B., Brady, S. W., Ma, X., Shen, S., Zhang, Y., Li, Y., Szlachta, K. A., Dong, L., Liu, Y., Yang, F., et al. (2019) · Blood · doi:10.1182/blood.2019002220 · Cited by 289 · see citing works
SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
Fedele, C., Li, S., Teng, K. W., Foster, C. J. R., Peng, D., Ran, H., Mita, P., Geer, M. J., Hattori, T., Koide, A., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201414 · Cited by 265 · see citing works
Mazhab-Jafari, M. T., Marshall, C. B., Smith, M. J., Gasmi-Seabrook, G. M. C., Stathopulos, P. B., Inagaki, F., Kay, L. E., Neel, B. G., & Ikura, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419895112 · Cited by 220 · see citing works
Serebriiskii, I. G., Connelly, C., Frampton, G., Newberg, J., Cooke, M., Miller, V., Ali, S., Ross, J. S., Handorf, E., Arora, S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11530-0 · Cited by 215 · see citing works
Caye‐Eude, A., Strullu, M., Guidez, F., Cassinat, B., Gazal, S., Fenneteau, O., Lainey, É., Nouri, K., Nakhaei‐Rad, S., Dvorský, R., et al. (2015) · Nature Genetics · doi:10.1038/ng.3420 · Cited by 190 · see citing works
Self-citationFunctional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes
Martinelli, S., Krumbach, O. H. F., Pantaleoni, F., Coppola, S., Amin, E., Pannone, L., Nouri, K., Farina, L., Dvorský, R., Lepri, F. R., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.12.015 · Cited by 195 · see citing works
Self-citationNovel Allosteric Sites on Ras for Lead Generation
Grant, B. J., Lukman, S., Hocker, H. J., Sayyah, J., Brown, J. H., McCammon, J. A., & Gorfe, A. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025711 · Cited by 178 · see citing works
The RASopathies: from pathogenetics to therapeutics
Hebron, K. E., Hernandez, E. R., & Yohe, M. E. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049107 · Cited by 167 · see citing works
Flex, E., Jaiswal, M., Pantaleoni, F., Martinelli, S., Strullu, M., Fansa, E. K., Caye‐Eude, A., Luca, A. D., Lepri, F. R., Dvorský, R., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu148 · Cited by 145 · see citing works
Self-citationHartmaier, R. J., Albacker, L. A., Chmielecki, J., Bailey, M., He, J., Goldberg, M. E., Ramkissoon, S. H., Suh, J. H., Elvin, J. A., Chiacchia, S., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2479 · Cited by 139 · see citing works
Classification of KRAS -Activating Mutations and the Implications for Therapeutic Intervention
Johnson, C. W., Burkhart, D. L., & Haigis, K. M. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0035 · Cited by 130 · see citing works
BRAF gene: From human cancers to developmental syndromes
Hussain, M. R. M., Baig, M., Mohamoud, H. S. A., Ul‐Haq, Z., Hoessli, D. C., Khogeer, G. S., Al-Sayed, R. R., & Al-Aama, J. Y. (2014) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2014.10.002 · Cited by 119 · see citing works
Motta, M., Fidan, M., Bellacchio, E., Pantaleoni, F., Schneider‐Heieck, K., Coppola, S., Borck, G., Salviati, L., Zenker, M., Cirstea, I. C., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy412 · Cited by 101 · see citing works
Self-citationK-Ras <sup>V14I</sup> recapitulates Noonan syndrome in mice
Hernández-Porras, I., Fabbiano, S., Schuhmacher, A. J., Aicher, A., Cañamero, M., Cámara, J. A., Cussó, L., Desco, M., Heeschen, C., Mulero, F., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418126111 · Cited by 96 · see citing works
Discovery of High-Affinity Noncovalent Allosteric KRAS Inhibitors That Disrupt Effector Binding
McCarthy, M. J., Pagba, C. V., Prakash, P., Naji, A. K., van der Hoeven, D., Liang, H., Gupta, A. K., Zhou, Y., Cho, K.-J., Hancock, J. F., et al. (2019) · ACS Omega · doi:10.1021/acsomega.8b03308 · Cited by 90 · see citing works
The Ras switch in structural and historical perspective
Gasper, R., & Wittinghofer, F. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0330 · Cited by 88 · see citing works
Pantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., & Poso, A. (2018) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1006458 · Cited by 85 · see citing works
Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome
Capri, Y., Flex, E., Krumbach, O. H. F., Carpentieri, G., Cecchetti, S., Lißewski, C., Adariani, S. R., Schanze, D., Brinkmann, J., Piard, J., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.04.013 · Cited by 78 · see citing works
Self-citationDifferences in the Regulation of K-Ras and H-Ras Isoforms by Monoubiquitination
Baker, R., Wilkerson, E., Sumita, K., Isom, D. G., Sasaki, A. T., Dohlman, H. G., & Campbell, S. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.c113.525691 · Cited by 77 · see citing works
Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering
Blaževitš, O., Mideksa, Y. G., Šolman, M., Ligabue, A., Ariotti, N., Nakhaeizadeh, H., Fansa, E. K., Papageorgiou, A. C., Wittinghofer, A., Ahmadian, M. R., et al. (2016) · Scientific Reports · doi:10.1038/srep24165 · Cited by 74 · see citing works
Self-citationBoppudi, S., Bögershausen, N., Hove, H., Perçin, E. F., Aslan, D., Dvorský, R., Kayhan, G., Li, Y., Cursiefen, C., Tantcheva‐Poór, I., et al. (2016) · Clinical Genetics · doi:10.1111/cge.12775 · Cited by 74 · see citing works
Self-citationGermline and sporadic cancers driven by the RAS pathway: parallels and contrasts
Dunnett-Kane, V., Burkitt-Wright, E., Blackhall, F. H., Malliri, A., Evans, D. G., & Lindsay, C. R. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.03.291 · Cited by 66 · see citing works
The RAS-Effector Interface: Isoform-Specific Differences in the Effector Binding Regions
Nakhaeizadeh, H., Amin, E., Nakhaei‐Rad, S., Dvorský, R., & Ahmadian, M. R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167145 · Cited by 70 · see citing works
Self-citationPetanidis, S., Anestakis, D., Argyraki, M., Hadzopoulou‐Cladaras, M., & Salifoglou, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073616 · Cited by 67 · see citing works
Structure‐energy‐based predictions and network modelling of RASopathy and cancer missense mutations
Kiel, C., & Serrano, L. G. (2014) · Molecular Systems Biology · doi:10.1002/msb.20145092 · Cited by 64 · see citing works
The effects of mutant Ras proteins on the cell signalome
Takács, T., Kudlik, G., Kurilla, A., Szeder, B., Buday, L., & Vas, V. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09912-8 · Cited by 62 · see citing works
Oncogenic mutant RAS signaling activity is rescaled by the ERK/MAPK pathway
Gillies, T. E., Pargett, M., Silva, J. M., Teragawa, C., McCormick, F. P., & Albeck, J. G. (2020) · Molecular Systems Biology · doi:10.15252/msb.20209518 · Cited by 54 · see citing works
How can same-gene mutations promote both cancer and developmental disorders?
Nussinov, R., Tsai, C., & Jang, H. (2022) · Science Advances · doi:10.1126/sciadv.abm2059 · Cited by 55 · see citing works
Genotype and phenotype spectrum of NRAS germline variants
Altmüller, F., Lißewski, C., Bertola, D. R., Flex, E., Stark, Z., Spranger, S., Baynam, G. S., Buscarilli, M., Dyack, S., Gillis, J., et al. (2017) · European Journal of Human Genetics · doi:10.1038/ejhg.2017.65 · Cited by 54 · see citing works
Self-citationŠolman, M., Ligabue, A., Blaževitš, O., Jaiswal, A., Zhou, Y., Hong, L., Lectez, B. L. P., Kopra, K., Guzmán, C., Härmä, H., et al. (2015) · eLife · doi:10.7554/elife.08905 · Cited by 50 · see citing works
Activating MRAS mutations cause Noonan syndrome associated with hypertrophic cardiomyopathy
Motta, M., Sagi‐Dain, L., Krumbach, O. H. F., Hahn, A., Peleg, A., German, A., Lißewski, C., Coppola, S., Pantaleoni, F., Kocherscheid, L., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz108 · Cited by 50 · see citing works
Self-citationComparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels
Kanavy, D., McNulty, S. M., Jairath, M. K., Brnich, S. E., Bizon, C., Powell, B. C., & Berg, J. S. (2019) · Genome Medicine · doi:10.1186/s13073-019-0683-1 · Cited by 50 · see citing works
Nussinov, R., Yavuz, B. R., Arici, M. K., Demirel, H. C., Zhang, M., Liu, Y., Tsai, C., Jang, H., & Tunçbağ, N. (2023) · Biophysical Reviews · doi:10.1007/s12551-023-01054-9 · Cited by 46 · see citing works
Miao, B., Niu, S., Wu, R., Liang, Z., Tang, B., Zhai, Y., & Xu, X. (2021) · Animals · doi:10.3390/ani11061745 · Cited by 48 · see citing works
Addissie, Y. A., Kotecha, U. H., Hart, R. A., Martinez, A. F., Kruszka, P. S., & Muenke, M. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37259 · Cited by 46 · see citing works
Cirstea, I. C., Gremer, L., Dvorský, R., Zhang, S.-C., Piekorz, R. P., Zenker, M., & Ahmadian, M. R. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds426 · Cited by 45 · see citing works
Self-citationZhao, X., Wang, A., Walter, V., Patel, N. M., Eberhard, D. A., Hayward, M. C., Salazar, A. H., Jo, H., Soloway, M. G., Wilkerson, M. D., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129280 · Cited by 42 · see citing works
Whitley, M. J., Tran, T. H., Rigby, M., Yi, M., Dharmaiah, S., Waybright, T. J., Ramakrishnan, N., Perkins, S. C., Taylor, T. E., Messing, S. A. J., et al. (2024) · Science Advances · doi:10.1126/sciadv.adj4137 · Cited by 39 · see citing works
Martinelli, S., Nardozza, A. P., Vigne, S. D., Sabetta, G., Torreri, P., Bocchinfuso, G., Flex, E., Venanzi, S., Palleschi, A., Gelb, B. D., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.350231 · Cited by 38 · see citing works
Hiatt, S. M., Neu, M. B., Ramaker, R. C., Hardigan, A. A., Prokop, J. W., Hančárová, M., Prchalová, D., Havlovičová, M., Prchal, J., Stránecký, V., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007671 · Cited by 35 · see citing works
Divergent Mechanisms Activating RAS and Small GTPases Through Post-translational Modification
Osaka, N., Hirota, Y., Ito, D., Ikeda, Y., Kamata, R., Fujii, Y., Chirasani, V. R., Campbell, S. L., Takeuchi, K., Senda, T., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.707439 · Cited by 33 · see citing works
Meng, X., Lu, J., Zeng, H., Chen, Z., Guo, X.-J., Gao, C., Pei, Y.-Z., Hu, S., Ye, M., Sun, Q., et al. (2022) · Hepatology International · doi:10.1007/s12072-022-10445-1 · Cited by 34 · see citing works
Rasopathies: Developmental Disorders That Predispose to Cancer and Skin Manifestations
Hernández‐Martín, A., & Torrelo, A. (2011) · Actas Dermo-Sifiliográficas · doi:10.1016/j.adengl.2011.02.002 · Cited by 33 · see citing works
Characterization of a novel KRAS mutation identified in Noonan syndrome
Razzaque, A. M., Komoike, Y., Nishizawa, T., Inai, K., Furutani, M., Higashinakagawa, T., & Matsuoka, R. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.34419 · Cited by 33 · see citing works
NRAS Mutations in Noonan Syndrome
Denayer, E., Peeters, H., Sevenants, L., Derbent, M., Fryns, J. P., & Legius, E. (2012) · Molecular Syndromology · doi:10.1159/000338467 · Cited by 32 · see citing works
Lorenz, S., Lißewski, C., Simsek-Kiper, P. O., Alanay, Y., Boduroğlu, K., Zenker, M., & Rosenberger, G. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt014 · Cited by 32 · see citing works
Self-citationRasopatías: trastornos del desarrollo con predisposición al cáncer y manifestaciones cutáneas
Hernández‐Martín, A., & Torrelo, A. (2011) · Actas Dermo-Sifiliográficas · doi:10.1016/j.ad.2011.02.010 · Cited by 30 · see citing works
Gripp, K. W., Sol‐Church, K., Smpokou, P., Graham, G. E., Stevenson, D. A., Hanson, H., Viskochil, D. H., Baker, L., Russo, B., Gardner, N., et al. (2015) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37128 · Cited by 30 · see citing works
Two novel germline KRAS mutations: expanding the molecular and clinical phenotype
Stark, Z., Gillessen‐Kaesbach, G., Ryan, M. M., Cirstea, I. C., Gremer, L., Ahmadian, M., Savarirayan, R., & Zenker, M. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01754.x · Cited by 30 · see citing works
Self-citationNakhaei‐Rad, S., Nakhaeizadeh, H., Götze, S., Kordes, C., Sawitza, I., Hoffmann, M. J., Franke, M., Schulz, W. A., Scheller, J., Piekorz, R. P., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.700088 · Cited by 31 · see citing works
Self-citationCYK-4 regulates Rac, but not Rho, during cytokinesis
Zhuravlev, Y., Hirsch, S. M., Jordan, S. N., Dumont, J., Shirasu‐Hiza, M., & Canman, J. C. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-01-0020 · Cited by 30 · see citing works
Structural basis of the atypical activation mechanism of KRASV14I
Bera, A. K., Lu, J., Wales, T. E., Gondi, S. R., Gurbani, D., Nelson, A., Engen, J. R., & Westover, K. D. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009131 · Cited by 30 · see citing works
Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects
Cao, Y., Chau, M. H. K., Zheng, Y., Zhao, Y., Kwan, A. H. W., Hui, S. Y. A., Lam, Y. H., Tan, T. Y. T., Tse, W. T., Wong, L., et al. (2022) · Prenatal Diagnosis · doi:10.1002/pd.6151 · Cited by 29 · see citing works
A graph theoretic approach to utilizing protein structure to identify non-random somatic mutations
Ryslik, G., Cheng, Y., Cheung, K.-H., Modis, Y., & Zhao, H. (2014) · BMC Bioinformatics · doi:10.1186/1471-2105-15-86 · Cited by 26 · see citing works
Klüppel, M., Samavarchi‐Tehrani, P., Liu, K., Wrana, J. L., & Hinek, A. (2012) · European Journal of Human Genetics · doi:10.1038/ejhg.2012.12 · Cited by 27 · see citing works
Distinct bilineal leukemia immunophenotypes are not genetically determined
Kotrová, M., Musilová, A., Stuchlý, J., Fišer, K., Starková, J., Mejstříková, E., Starý, J., Zuna, J., Hrušák, O., Trka, J., et al. (2016) · Blood · doi:10.1182/blood-2016-07-725861 · Cited by 26 · see citing works
RAS‐targeted cancer therapy: Advances in drugging specific mutations
Liu, C., Ye, D., Yang, H., Chen, X., Su, Z., Li, X., Ding, M., & Liu, Y. (2023) · MedComm · doi:10.1002/mco2.285 · Cited by 24 · see citing works
Bertola, D. R., Pereira, A., Brasil, A., Suzuki, L., Leite, C. C., Falzoni, R., Tannuri, U., Poplawski, A. B., Janowski, K., Kim, C. A., et al. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01764.x · Cited by 25 · see citing works
KrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice
Wong, J. C. Y., Pérez-Mancera, P. A., Huang, T. Q., Kim, J., Grego‐Bessa, J., Alzamora, M. D. P., Kogan, S. C., Sharir, A., Keefe, S. H., Morales, C. E., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.140495 · Cited by 24 · see citing works
Self-citationBiochemical Assays to Characterize Rho GTPases
Jaiswal, M., Dubey, B. N., Koessmeier, K. T., Gremer, L., & Ahmadian, M. R. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-442-1_3 · Cited by 24 · see citing works
Self-citationBrasil, A. S., Malaquias, A. C., Kim, C. A., Krieger, J. E., Jorge, A. A. L., Pereira, A. C., & Bertola, D. R. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35270 · Cited by 23 · see citing works
Adariani, S. R., Jasemi, N. S. K., Bazgir, F., Wittich, C., Amin, E., Seidel, C. A. M., Dvorský, R., & Ahmadian, M. R. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100626 · Cited by 23 · see citing works
Self-citationSuzuki, H., Takenouchi, T., Uehara, T., Takasago, S., Ihara, S., Yoshihashi, H., & Kosaki, K. (2019) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61261 · Cited by 23 · see citing works
Landscape of Genetic Mutations in Appendiceal Cancers
Constantin, M., Mătanie, C., Petrescu, L., Bolocan, A., Andronic, O., Bleoţu, C., Mitache, M. M., Tudorache, S. I., & Vrâncianu, C. O. (2023) · Cancers · doi:10.3390/cancers15143591 · Cited by 22 · see citing works
Zong, X., Zhang, Y., Peng, X., Cao, D., Yu, M. Y., Wang, J., Li, H., Guo, X., Liang, H., & Yang, J. (2021) · Nature Communications · doi:10.1038/s41467-021-23681-0 · Cited by 21 · see citing works
New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling
Erickson, K. E., Rukhlenko, O. S., Posner, R. G., Hlavacek, W. S., & Kholodenko, B. Ν. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.02.008 · Cited by 20 · see citing works
Splice variants of RAS—translational significance
Rásó, E. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09920-8 · Cited by 19 · see citing works
Senescence in RASopathies, a possible novel contributor to a complex pathophenoype
Engler, M., Fidan, M., Nandi, S., & Cirstea, I. C. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111411 · Cited by 15 · see citing works
Self-citationReview of ferroptosis in colorectal cancer: Friends or foes?
Wu, Z., Fang, Z.-X., Hou, Y.-Y., Wu, B., Deng, Y., Wu, H.-T., & Liu, J. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i3.469 · Cited by 18 · see citing works
Fang, Z., Marshall, C. B., Yin, J. C., Mazhab‐Jafari, M. T., Gasmi-Seabrook, G. M. C., Smith, M. J., Nishikawa, T., Xu, Y., Neel, B. G., & Ikura, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.714196 · Cited by 18 · see citing works
Emerging Targeted Therapy for Specific Genomic Abnormalities in Acute Myeloid Leukemia
Chi, S., & Minami, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042362 · Cited by 16 · see citing works
Gripp, K. W., Hopkins, E., Serrano, A., Leonard, N., Stabley, D. L., & Sol‐Church, K. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35294 · Cited by 18 · see citing works
Wilcox, E. H., Webb, R., Tshering, K. C., Hughes, M. Y., Cavé, H., DiStefano, M. T., Dziadzio, H., Garber, K., Gelb, B. D., Gripp, K. W., et al. (2025) · Genetics in Medicine Open · doi:10.1016/j.gimo.2025.103430 · Cited by 17 · see citing works
Self-citationLYMPHODYSPLASIA AND KRAS MUTATION: A CASE REPORT AND LITERATURE REVIEW.
Morcaldi, G., Bellini, T., Rossi, C., Maghnie, M., Boccardo, F. M., Bonioli, E., & Bellini, C. (2015) · PubMed · Cited by 17 · see citing works
Pantaleoni, F., Lev, D., Cirstea, I. C., Motta, M., Lepri, F. R., Bottero, L., Cecchetti, S., Linger, I., Paolacci, S., Flex, E., et al. (2017) · Human Mutation · doi:10.1002/humu.23224 · Cited by 17 · see citing works
Self-citationK‐<scp>Ras<sup>V14I</sup></scp>‐induced Noonan syndrome predisposes to tumour development in mice
Hernández‐Porras, I., Schuhmacher, A. J., Garcia‐Medina, R., Jiménez, B., Cañamero, M., de Martino, A., & Guerra, C. (2016) · The Journal of Pathology · doi:10.1002/path.4719 · Cited by 16 · see citing works
Neuron type-specific expression of a mutant KRAS impairs hippocampal-dependent learning and memory
Ryu, H.-H., Kang, M., Hwang, K., Jang, H. B., Kim, S. J., & Lee, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-74610-y · Cited by 16 · see citing works
Nakhaei‐Rad, S., Nakhaeizadeh, H., Kordes, C., Cirstea, I. C., Schmick, M., Dvorský, R., Bastiaens, P. I. H., Häussinger, D., & Ahmadian, M. R. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.640607 · Cited by 15 · see citing works
Self-citationClinical profiling of MRD48 and functional characterization of two novel pathogenic RAC1 variants
Priolo, M., Zara, E., Radio, F. C., Ciolfi, A., Spadaro, F., Bellacchio, E., Mancini, C., Pantaleoni, F., Cordeddu, V., Chiriatti, L., et al. (2023) · European Journal of Human Genetics · doi:10.1038/s41431-023-01351-7 · Cited by 15 · see citing works
Genomic landscape of gallbladder cancer: insights from whole exome sequencing
Awasthi, S., Kumar, R., Pradhan, D., Rawal, N., Goel, H., Sahu, P., Sisodiya, S., Rana, R., Kumar, S., Dash, N. R., et al. (2024) · International Journal of Surgery · doi:10.1097/js9.0000000000002031 · Cited by 13 · see citing works
Identification of lysine methylation in the core GTPase domain by GoMADScan
Yoshino, H., Yin, G., Kawaguchi, R. K., Popov, K. I., Temple, B. R. S., Sasaki, M., Kofuji, S., Wolfe, K., Kofuji, K., Okumura, K., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0219436 · Cited by 13 · see citing works
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Hiippala, A., Vasilescu, C., Tallila, J., Alastalo, T., Paetau, A. E., Tyni, T. A., Suomalainen, A., Euro, L., & Ojala, T. H. (2016) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.37596 · Cited by 12 · see citing works
Kwon, J. J., Dilly, J., Liu, S., Kim, E., Bian, Y., Dharmaiah, S., Tran, T. H., Kapner, K. S., Ly, S. H., Yang, X., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.22.618529 · Cited by 11 · see citing works
Nosan, G., Bertok, S., Vesel, S., Yntema, H. G., & Paro‐Panjan, D. (2013) · Croatian Medical Journal · doi:10.3325/cmj.2013.54.574 · Cited by 10 · see citing works
Beyens, A., Dequeker, L., Brems, H., Janssens, S., Syryn, H., D’Hooghe, A., Paepe, P. D., Vanwalleghem, L., Stockman, A., Vankwikelberge, E., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23074036 · Cited by 10 · see citing works
Bohn, E., Lau, T. T. Y., Wagih, O., Masud, T., & Merico, D. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1257550 · Cited by 10 · see citing works
Merlin cooperates with neurofibromin and Spred1 to suppress the Ras–Erk pathway
Cui, Y., Ma, L., Schacke, S., Yin, J. C., Hsueh, Y., Jin, H., & Morrison, H. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa263 · Cited by 10 · see citing works
Nagai, K., Niihori, T., Okamoto, N., Kondo, A., Suga, K., Ohhira, T., Hayabuchi, Y., Homma, Y., Nakagawa, R., Ifuku, T., et al. (2021) · Human Mutation · doi:10.1002/humu.24287 · Cited by 10 · see citing works
New mechanistic insights into the RAS-SIN1 interaction at the membrane
Pudewell, S., Lissy, J., Nakhaeizadeh, H., Mosaddeghzadeh, N., Nakhaei‐Rad, S., Dvorský, R., & Ahmadian, M. R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.987754 · Cited by 10 · see citing works
Self-citationSana, M. E., Quilliam, L. A., Spitaleri, A., Pezzoli, L., Marchetti, D., Lodrini, C., Candiago, E., Lincesso, A. R., Ferrazzi, P., & Iascone, M. R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0168501 · Cited by 10 · see citing works
Yang, C., Li, H.-X., Gan, H., Shuai, X., Dong, C., Wang, W. J., Lin, D., & Zhong, B. (2025) · Developmental Cell · doi:10.1016/j.devcel.2025.01.015 · Cited by 9 · see citing works
From mutations to mechanisms and dysfunction via computation and mining of protein energy landscapes
Qiao, W., Akhter, N., Fang, X., Maximova, T., Plaku, E., & Shehu, A. (2018) · BMC Genomics · doi:10.1186/s12864-018-5024-z · Cited by 9 · see citing works
RAS-pathies: Noonan syndrome and other related diseases. The literature review
Faassen, M. V. (2014) · Problems of Endocrinology · doi:10.14341/probl201460645-52 · Cited by 10 · see citing works
Chippalkatti, R., Parisi, B., Kouzi, F., Laurini, C., Fredj, N. B., & Abankwa, D. (2024) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2024.151425 · Cited by 8 · see citing works
Single nucleotide variants in lung cancer
Tian, X., & Liu, Z. (2024) · Chinese Medical Journal - Pulmonary and Critical Care Medicine · doi:10.1016/j.pccm.2024.04.004 · Cited by 8 · see citing works
- Authors
- Gremer, L., Merbitz-Zahradnik, T., Dvorsky, R., Cirstea, I. C., Kratz, C. P., Zenker, M., Wittinghofer, A., & Ahmadian, M. R.
- Affiliations
- Max Planck Institute of Molecular Physiology (DE)
- Heinrich Heine University Düsseldorf (DE)
- National Institutes of Health (US)
- University Hospital Magdeburg (DE)
- Corresponding author
- Ahmadian, Mohammad Reza
- ORCID
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2010-12-09
- Volume
- 32
- Issue
- 1
- Pages
- 33-43
- ISSN
- 1059-7794 (ISSN-L)
- PMC
- PMC3117284
- OpenAlex
- W2053733865
- Cited by
- 158
- References
- 93
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 18 · 2023: 14 · 2022: 13 · 2021: 9 · 2020: 14 · 2019: 10 · 2018: 8 · 2017: 11 · 2016: 11 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 8
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- E-Rare
- Deutsche Forschungsgemeinschaft (AH 92/5-1)
- Bundesministerium für Bildung und Forschung (01GS08100)
- National Institutes of Health
- National Cancer Institute (ZIACP010144)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, oncogenic Ras, GTPase activity, guanine nucleotide exchange, GTP hydrolysis, phenotypic variability, developmental disorders, protein structure
- MeSH terms
- Animals, Chlorocebus aethiops, Developmental Disabilities, Ectodermal Dysplasia, Failure to Thrive, Heart Defects, Congenital, Humans, Models, Molecular, Noonan Syndrome, Proto-Oncogene Proteins, Signal Transduction, Proto-Oncogene Proteins p21(ras), Germ-Line Mutation, ras Proteins, Facies, COS Cells, GTPase-Activating Proteins
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