Heat-shock protein hsp90 governs the activity of pp60v-src kinase.
Open accessAbstract
During or immediately after synthesis in vertebrate cells, the oncogenic protein-tyrosine kinase pp60v-src associates with the approximately 90-kDa heat-shock protein (hsp90). In this complex, pp60v-src is not functional as a kinase. When pp60v-src is subsequently found inserted into the plasma membrane, it is active as a kinase and is no longer associated with hsp90. We have taken advantage of genetic manipulations possible in Saccharomyces cerevisiae to investigate the function and specificity of the association between hsp90 and pp60v-src. Expression of pp60v-src is known to be toxic to S. cerevisiae cells. We find that this toxicity is due to a very specific effect on growth, arrest at a particular point in the cell cycle. In cells expressing v-src, a mutation that lowers the level of hsp90 expression (i) relieves cell cycle arrest and rescues growth, (ii) reduces the level of tyrosine phosphorylation mediated by pp60v-src, (iii) changes the pattern of tyrosine phosphorylation, and (iv) reduces the concentration of pp60v-src. We conclude that hsp90 does not simply suppress pp60v-src kinase activity during transit to the plasma membrane, as previously suggested, but also stabilizes the protein and affects both its activity and specificity. This function of hsp90 is highly selective for pp60v-src: the same hsp90 mutation has no effect on the activity or specificity of the exogenous pp160v-abl tyrosine kinase; similarly, it does not affect the specificity and has only a very small effect on the activity of the exogenous pp60c-src kinase.
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Hsp90's role as a potentiator for genetic variation has been observed in fungi as well as mammalian cancer cells.
“This role as a potentiator for genetic variation has been observed in fungi as well as mammalian cancer cells20,88,135,136.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [136]
Hsp90 can enable the phenotypic effects of new mutations either by stabilizing mutant regulators or by stabilizing non-mutant regulators that mediate signalling required for adaptation.
“Second, Hsp90 can enable the phenotypic effects of new mutations either by stabilizing mutant regulators or by stabilizing non-mutant regulators that mediate signalling required for adaptation.”
From Fungal Hsp90: a biological transistor that tunes cellular outputs to thermal inputs (2012) · cites this paper as [136]
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Cites
Transformation of intact yeast cells treated with alkali cations
Ito, H., Fukuda, Y., Murata, K., & Kimura, A. (1983) · Journal of Bacteriology · doi:10.1128/jb.153.1.163-168.1983 · Cited by 7,518 · see citing works
Lindquist, S., & Craig, E. A. (1988) · Annual Review of Genetics · doi:10.1146/annurev.ge.22.120188.003215 · Cited by 5,304 · see citing works
Self-citation[12] One-step gene disruption in yeast
Rothstein, R. J. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)01015-0 · Cited by 3,282 · see citing works
SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins
Koch, C. A., Anderson, D. H., Moran, M. F., Ellis, C. A., & Pawson, T. J. (1991) · Science · doi:10.1126/science.1708916 · Cited by 1,868 · see citing works
Reduced levels of hsp90 compromise steroid receptor action in vivo
Picard, D., Khursheed, B., Garabedian, M. J., Fortin, M. G., Lindquist, S., & Yamamoto, K. R. (1990) · Nature · doi:10.1038/348166a0 · Cited by 787 · see citing works
Self-citationBorkovich, K. A., Farrelly, F. W., Finkelstein, D. B., Taulien, J., & Lindquist, S. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3919 · Cited by 641 · see citing works
Self-citationSteroid receptors and their associated proteins
Smith, D. F., & Toft, D. O. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.1.8446107 · Cited by 549 · see citing works
Peptides and Protein Phosphorylation
Kemp, B. E. (2018) · CRC Press eBooks · doi:10.1201/9781351075442 · Cited by 522 · see citing works
Hsp90 chaperones protein folding in vitro
Wiech, H., Büchner, J., Zimmermann, R., & Jakob, U. (1992) · Nature · doi:10.1038/358169a0 · Cited by 505 · see citing works
Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses
Lipsich, L. A., Lewis, A., & Brugge, J. S. (1983) · Journal of Virology · doi:10.1128/jvi.48.2.352-360.1983 · Cited by 494 · see citing works
Kawai, S., & Hanafusa, H. (1971) · Virology · doi:10.1016/0042-6822(71)90047-x · Cited by 399 · see citing works
Williamson, D. H., & Fennell, D. J. (1975) · Methods in cell biology · doi:10.1016/s0091-679x(08)60963-2 · Cited by 365 · see citing works
Brugge, J. S., ERIKSON, E., & Erikson, R. L. (1981) · Cell · doi:10.1016/0092-8674(81)90055-6 · Cited by 362 · see citing works
Identification of a 60-Kilodalton Stress-Related Protein, p60, which Interacts with hsp90 and hsp70
Smith, D. F., Sullivan, W. P., Marion, T. N., Zaitsu, K., Madden, B. J., McCormick, D., & Toft, D. O. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.2.869 · Cited by 269 · see citing works
DNA sequences homologous to vertebrate oncogenes are conserved in Drosophila melanogaster.
Shilo, B., & Weinberg, R. A. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6789 · Cited by 263 · see citing works
Borkovich, K. A., Farrelly, F. W., FINKELSTEIN, D. B., et al. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.9.3919-3930.1989 · Cited by 255 · see citing works
Oppermann, H., Levinson, W. E., & Bishop, J. M. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.2.1067 · Cited by 249 · see citing works
Iba, H., Takeya, T., Cross, F. R., Hanafusa, T., & Hanafusa, H. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.14.4424 · Cited by 230 · see citing works
Interaction of the Rous Sarcoma Virus Protein pp60 src with the Cellular Proteins pp50 and pp90
Brugge, J. S. (1986) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-70810-7_1 · Cited by 225 · see citing works
The nucleotide sequence and the tissue-specific expression of Drosophila c-src
Simon, M. A., Drees, B., Kornberg, T. B., & Bishop, J. M. (1985) · Cell · doi:10.1016/0092-8674(85)90279-x · Cited by 196 · see citing works
Genetics of src: Structure and Functional Organization of a Protein Tyrosine Kinase
Parsons, J. T., & Weber, M. J. (1989) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-74697-0_3 · Cited by 196 · see citing works
Structural and functional reconstitution of the glucocorticoid receptor-hsp90 complex.
Scherrer, L. C., Dalman, F. C., Massa, E., Meshinchi, S., & Pratt, W. B. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45746-8 · Cited by 186 · see citing works
Snyder, M. A., Bishop, J. M., McGrath, J. P., & Levinson, A. D. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.7.1772 · Cited by 126 · see citing works
Jove, R., Kornbluth, S. A., & Hanafusa, H. (1987) · Cell · doi:10.1016/0092-8674(87)90520-4 · Cited by 116 · see citing works
Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell-free system.
Hutchison, K. A., Brott, B. K., de León, J. H., Perdew, G. H., Jove, R., & Pratt, W. B. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50671-8 · Cited by 93 · see citing works
Falk, H., Einat, P., Shilo, B., & Hoffmann, F. M. (1983) · Cell · doi:10.1016/0092-8674(83)90478-6 · Cited by 88 · see citing works
Characterization of avian and viral p60src proteins expressed in yeast.
Kornbluth, S. A., Jove, R., & Hanafusa, H. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.13.4455 · Cited by 86 · see citing works
Pratt, W. B., Sánchez, E. R., Bresnick, E. H., Meshinchi, S., Scherrer, L. C., Dalman, F. C., & Welsh, M. J. (1989) · PubMed · Cited by 75 · see citing works
Protein-Tyrosine Kinase Activity in Saccharomyces cerevisiae
Schieven, G. L., Thorner, J. W., & Martin, G. S. (1986) · Science · doi:10.1126/science.2417318 · Cited by 66 · see citing works
Expression of Rous sarcoma virus transforming protein pp60v-src in Saccharomyces cerevisiae cells.
Brugge, J. S., Jarosik, G. P., Andersen, J., Queral-Lustig, A. E., Fedor‐Chaiken, M., & Broach, J. R. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.6.2180 · Cited by 65 · see citing works
Drosophila abl and genetic redundancy in signal transduction
HOFFMANN, F. (1991) · Trends in Genetics · doi:10.1016/0168-9525(91)90254-f · Cited by 62 · see citing works
Adkins, B., Hunter, T. R., & Sefton, B. M. (1982) · Journal of Virology · doi:10.1128/jvi.43.2.448-455.1982 · Cited by 49 · see citing works
Identification of a 60-Kilodalton Stress-Related Protein, p60, which Interacts with hsp90 and hsp70
Smith, D. F., Sullivan, W. P., Marion, T. N., et al. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.2.869-876.1993 · Cited by 48 · see citing works
Snyder, M. A., Bishop, J. M., McGrath, J. P., & Levinson, A. D. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.7.1772-1779.1985 · Cited by 39 · see citing works
Expression of Rous Sarcoma Virus Transforming Protein pp60v-src in Saccharomyces cerevisiae Cells
Brugge, J. S., Jarosik, G. P., Andersen, J., Queral-Lustig, A. E., Fedor‐Chaiken, M., & Broach, J. R. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.6.2180-2187.1987 · Cited by 28 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- [3]Shilo, B. Z. & Weinberg, R. A. (1981) Proc. Natl. Acad. Sci. USA 78, 6789–6792.
- [8]Iba, H., Takeya, T., Cross, F. R., Hanafusa, T. & Hanafusa, H. (1984) Proc. Natl. Acad. Sci. USA 81, 4424–4428.
- [13]Oppermann, H., Levinson, W. & Bishop, J. M. (1981) Proc. Natl. Acad. Sci. USA 78, 1067–1071.
- [24]Kornbluth, S., Jove, R. & Hanafusa, H. (1987) Proc. Natl. Acad. Sci. USA 84, 4455–4459.
Cited by
Sorted by citations
HSP90 and the chaperoning of cancer
Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502 · see citing works
“Using genetic and pharmacological approaches, this aberrant chaperone interaction was eventually shown to be essential for both acquisition and maintenance of the increased kinase activity that underlies the transforming activity of v-SR”
BackgroundSelf-citationHsp90 as a capacitor for morphological evolution
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270 · see citing works
Self-citationHSP90 at the hub of protein homeostasis: emerging mechanistic insights
Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818 · see citing works
“Studies with Rous sarcoma virus showed that although v-Src robustly bound HSP90, its normal cellular counterpart, c-Src (which has ∼98% sequence identit”
BackgroundSelf-citationSchopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540 · see citing works
Pratt, W., & Toft, D. (2003) · Experimental biology and medicine · doi:10.1177/153537020322800201 · Cited by 1,539 · see citing works
Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E., & Neckers, L. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8324 · Cited by 1,444 · see citing works
Interaction of 14-3-3 with Signaling Proteins Is Mediated by the Recognition of Phosphoserine
Muslin, A. J., Tanner, J. W., Allen, P. M., & Shaw, A. S. (1996) · Cell · doi:10.1016/s0092-8674(00)81067-3 · Cited by 1,380 · see citing works
Stebbins, C. E., Russo, A. A., Schneider, C. B., Rosen, N. X., Hartl, F. U., & Pavletich, N. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80203-2 · Cited by 1,370 · see citing works
“aforementioned protein kinases has been demonstrated both genetically (Xu and Lindquist, 1993; Aligue et al., 1994; Nathan and Lindquist, 1995) and biochemically ‖ These authors contributed equally to this work.”
Folding of Newly Translated Proteins In Vivo: The Role of Molecular Chaperones
Frydman, J. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.603 · Cited by 1,170 · see citing works
Heat Shock Protein 70 kDa Molecular Biology, Biochemistry, and Physiology
Kiang, J. G. (1998) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(98)00028-x · Cited by 1,164 · see citing works
Role of the Heat Shock Response and Molecular Chaperones in Oncogenesis and Cell Death
Jolly, C. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.19.1564 · Cited by 1,049 · see citing works
The 90-kDa Molecular Chaperone Family
Csermely, P., Schnaider, T., Sőti, C., Prohászka, Z., & Nardai, G. (1998) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(98)00013-8 · Cited by 1,024 · see citing works
“hsp90 is necessary for the correct folding, and thus, for the activity of many of these kinases, such as the v-Src kinase (Xu and Lindquist, 1993; Nathan and Lindquist, 1995), the Raf kinase (van der Straten et al.”
Dynamic activation of endothelial nitric oxide synthase by Hsp90
García‐Cardeña, G., Fan, R., Shah, V. H., Sorrentino, R., Cirino, G., Papapetropoulos, A., & Sessa, W. C. (1998) · Nature · doi:10.1038/33934 · Cited by 1,029 · see citing works
Young, J. C., Moarefi, I., & Hartl, F. U. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200104079 · Cited by 826 · see citing works
“, 1990; for review see Pratt and Toft, 1997), several tyrosine and serine/ threonine kinases such as pp60/v-src, Wee-1, Cdk4, and Raf (Xu and Lindquist, 1993; Aligue et al., 1994; Stepanova et al., 1996; van der Straten et al., 1997), and disparate proteins such as nitric oxide synthase and calcineurin (Garon S etem e…”
BackgroundInfluentialHsp90 Potentiates the Rapid Evolution of New Traits: Drug Resistance in Diverse Fungi
Cowen, L. E., & Lindquist, S. (2005) · Science · doi:10.1126/science.1118370 · Cited by 698 · see citing works
Self-citationHsp90 inhibitors as novel cancer chemotherapeutic agents
Neckers, L. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02316-x · Cited by 677 · see citing works
Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1α-degradative pathway
Isaacs, J. S., Jung, Y.-J., Mimnaugh, E. G., Martinez, A., Cuttitta, F., & Neckers, L. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204733200 · Cited by 663 · see citing works
Chaperoning signaling pathways: molecular chaperones as stress-sensing`heat shock' proteins
Nollen, E. A. A., & Morimoto, R. I. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.14.2809 · Cited by 644 · see citing works
Pratt, W. B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80556-0 · Cited by 644 · see citing works
Hsp90 & Co. – a holding for folding
Büchner, J. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01373-0 · Cited by 625 · see citing works
Hsp70 and Hsp90—a relay team for protein folding
Wegele, H., Müller, L., & Büchner, J. (2004) · Springer eBooks · doi:10.1007/s10254-003-0021-1 · Cited by 603 · see citing works
Molecular chaperones and protein folding in plants
Boston, R. S., Viitanen, P. V., & Vierling, E. (1996) · Plant Molecular Biology · doi:10.1007/bf00039383 · Cited by 600 · see citing works
Eustace, B. K., Sakurai, T., Stewart, J. K., Yimlamai, D., Unger, C., Zehetmeier, C., Lain, B., Torella, C., Henning, S. W., Beste, G., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1131 · Cited by 590 · see citing works
Pandey, P., Saleh, A., Nakazawa, A., Kumar, S., Srinivasula, S. M., Kumar, V., Weichselbaum, R. R., Nalin, C. M., Alnemri, E. S., Kufe, D. W., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.16.4310 · Cited by 556 · see citing works
Wandinger, S. K., Richter, K., & Büchner, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r800007200 · Cited by 548 · see citing works
Muise‐Helmericks, R. C., Grimes, H. L., Bellacosa, A., Malstrom, S. E., Tsichlis, P. N., & Rosen, N. X. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29864 · Cited by 511 · see citing works
The Hsp90 chaperone machinery: Conformational dynamics and regulation by co-chaperones
Li, J., Soroka, J., & Buchner, J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.09.003 · Cited by 498 · see citing works
Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4
Stepanova, L., Leng, X., Parker, S. B., & Harper, J. W. (1996) · Genes & Development · doi:10.1101/gad.10.12.1491 · Cited by 483 · see citing works
Schulte, T. W., Blagosklonny, M. V., Ingui, C., & Neckers, L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.24585 · Cited by 457 · see citing works
Mutational Analysis of Hsp90 Function: Interactions with a Steroid Receptor and a Protein Kinase
Nathan, D. F., & Lindquist, S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.7.3917 · Cited by 423 · see citing works
Self-citationProtein Folding in the Cytoplasm and the Heat Shock ResponsePreprint
Vabulas, R. M., Raychaudhuri, S., Hayer-Hartl, M. K., & Hartl, F. U. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004390 · Cited by 425 · see citing works
“For example, the exchange of only a few amino acids in the viral v-Src renders this kinase strongly dependent on Hsp90 as compared with the cellular c-Src variant (Xu and Lindquist 1993; Falsone et al. 2004).”
BackgroundFreeman, B. C., & Morimoto, R. I. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00660.x · Cited by 424 · see citing works
An Acetylation Site in the Middle Domain of Hsp90 Regulates Chaperone Function
Scroggins, B. T., Robzyk, K., Wang, D., Marcu, M. G., Tsutsumi, S., Beebe, K., Cotter, R. J., Felts, S., Toft, D., Karnitz, L., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.12.008 · Cited by 413 · see citing works
“This has been used as a phenotypic readout of the ability of various Hsp90 mutants to chaperone p60v-Src in yeast (Nathan and Lindquist, 1995; Xu and Lindquist, 1993).”
Method<i>In vivo</i> functions of the <i>Saccharomyces cerevisiae</i> Hsp90 chaperone
Nathan, D. F., Vos, M. H., & Lindquist, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.12949 · Cited by 364 · see citing works
Self-citationTransient Interaction of Hsp90 with Early Unfolding Intermediates of Citrate Synthase
Jakob, U., Lilie, H., Meyer, I., & Büchner, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7288 · Cited by 360 · see citing works
The Mechanism of Hsp90 Regulation by the Protein Kinase-Specific Cochaperone p50cdc37
Roe, S. M., Ali, M. M. U., Meyer, P., Vaughan, C. K., Panaretou, B., Piper, P. W., Prodromou, C., & Pearl, L. H. (2004) · Cell · doi:10.1016/s0092-8674(03)01027-4 · Cited by 351 · see citing works
Pratt, W. B. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.297 · Cited by 335 · see citing works
Birnby, D., Link, E. M., Vowels, J. J., Tian, H., Colacurcio, P. L., & Thomas, J. H. (2000) · Genetics · doi:10.1093/genetics/155.1.85 · Cited by 328 · see citing works
Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90.
Blagosklonny, M. V., Toretsky, J. A., Bohen, S. P., & Neckers, L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8379 · Cited by 315 · see citing works
Aneuploidy causes proteotoxic stress in yeastPreprint
Oromendia, A. B., Dodgson, S. E., & Amon, A. (2012) · Genes & Development · doi:10.1101/gad.207407.112 · Cited by 307 · see citing works
The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype.
Cowen, L. E. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1835 · Cited by 311 · see citing works
Hu, J.-M., Toft, D., & Seeger, C. (1997) · EMBO Journal · doi:10.1093/emboj/16.1.59 · Cited by 328 · see citing works
“…assembly and priming of viral DNA Courtneidge and Bishop, 1982; Hutchison et al., 1992; synthesis where a dynamic, energy-driven process, Xu and Lindquist, 1993) and, in vitro, the refolding of mediated by a multi-component chaperone complex denatured proteins (Wiech et al., 1992; Jakob…”
BackgroundMechanisms of protein-folding diseases at a glance
Valastyan, J. S., & Lindquist, S. L. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.013474 · Cited by 307 · see citing works
Self-citationGeldanamycin as a Potential Anti-Cancer Agent: Its Molecular Target and Biochemical Activity
Neckers, L., Schulte, T. W., & Mimnaugh, E. G. (1999) · Investigational New Drugs · doi:10.1023/a:1006382320697 · Cited by 300 · see citing works
“Also, c-Src expressed in yeast was not destabilized or inactivated in an Hsp90-deficient mutant [18].”
BackgroundBetween genotype and phenotype: protein chaperones and evolvability
Rutherford, S. L. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1041 · Cited by 292 · see citing works
“From signal transduction to threshold traits If HSP90 is impaired in cells, signal-transduction targets begin to lose functio”
BackgroundStructure of an Hsp90-Cdc37-Cdk4 Complex
Vaughan, C. K., Gohlke, U., Sobott, F., Good, V. M., Ali, M. M. U., Prodromou, C., Robinson, C. V., Saibil, H. R., & Pearl, L. H. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.07.016 · Cited by 293 · see citing works
“…Raf-1 (Grammatikakis et al., 1999; Schulte et al., 1995; Stancato et al., 1993), ErbB2 (Xu et al., 2001), Src-family kinases (Bijlmakers and Marsh, 2000; Xu and Lindquist, 1993; Xu et al., 1999), Aurora B (Lange et al., 2002), RIP (Lewis et al., 2000), components of the IkB kinase complex (Chen et…”
BackgroundCutforth, T. (1994) · Cell · doi:10.1016/0092-8674(94)90442-1 · Cited by 287 · see citing works
Mice lacking HSP90β fail to develop a placental labyrinth
Voss, A. K., Thomas, T., & Gruß, P. (2000) · Development · doi:10.1242/dev.127.1.1 · Cited by 282 · see citing works
Chaperones in cell cycle regulation and mitogenic signal transduction: a review
Helmbrecht, K., Zeise, E., & Rensing, L. (2000) · Cell Proliferation · doi:10.1046/j.1365-2184.2000.00189.x · Cited by 278 · see citing works
“2; Xu & Lindquist 1993).”
BackgroundInfluentialThe chaperone Hsp90: changing partners for demanding clients
Röhl, A., Rohrberg, J., & Büchner, J. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.02.003 · Cited by 268 · see citing works
Song, H. Y., Dunbar, J. D., Zhang, Y. X., Guo, D., & Donner, D. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.8.3574 · Cited by 266 · see citing works
An, W. G., Schulte, T. W., & Neckers, L. Μ. (2000) · PubMed · Cited by 265 · see citing works
Gravitropism in Higher Plants1
Chen, R., Rosen, E., & Masson, P. (1999) · PLANT PHYSIOLOGY · doi:10.1104/pp.120.2.343 · Cited by 264 · see citing works
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BackgroundAligue, R., Akhavan‐Niak, H., & Russell, P. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06956.x · Cited by 261 · see citing works
The native structure of the activated Raf protein kinase is a membrane-bound multi-subunit complex.
Wartmann, M., & Davis, R. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37431-8 · Cited by 261 · see citing works
On the origins of novelty in development and evolution
Moczek, A. P. (2008) · BioEssays · doi:10.1002/bies.20754 · Cited by 252 · see citing works
Nimmanapalli, R., O’Bryan, E., & Bhalla, K. N. (2001) · PubMed · Cited by 243 · see citing works
Two chaperone sites in Hsp90 differing in substrate specificity and ATP dependence
Scheibel, T., Weikl, T., & Buchner, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1495 · Cited by 243 · see citing works
Stimulation of the weak ATPase activity of human hsp90 by a client protein.
McLaughlin, S., Smith, H. W., & Jackson, S. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5245 · Cited by 244 · see citing works
Lotz, G. P., Lin, H., Harst, A., & Obermann, W. M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212761200 · Cited by 236 · see citing works
Role of the Protein Chaperone YDJ1 in Establishing Hsp90-Mediated Signal Transduction Pathways
Kimura, Y., Yahara, I., & Lindquist, S. L. (1995) · Science · doi:10.1126/science.7761857 · Cited by 228 · see citing works
Self-citationA Cyclophilin Function in Hsp90-Dependent Signal Transduction
Duina, A. A., Foreman, H.-C. C., Marsh, J. A., Lindquist, S. L., & Gaber, R. F. (1996) · Science · doi:10.1126/science.274.5293.1713 · Cited by 224 · see citing works
Self-citationIn Vivo Analysis of the Hsp90 Cochaperone Sti1 (p60)
Foreman, H.-C. C., Nathan, D. F., & Lindquist, S. L. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.1.318 · Cited by 214 · see citing works
Self-citationCdc37 is a molecular chaperone with specific functions in signal transduction.Preprint
Kimura, Y., Rutherford, S. L., Miyata, Y., Yahara, I., Freeman, B. C., Yue, L., Morimoto, R. I., & Lindquist, S. (1997) · Genes & Development · doi:10.1101/gad.11.14.1775 · Cited by 206 · see citing works
Self-citationHSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes
Zhu, D., Dix, D. J., & Eddy, E. M. (1997) · Development · doi:10.1242/dev.124.15.3007 · Cited by 205 · see citing works
Vaughan, C. K., Mollapour, M., Smith, J. R., Truman, A. W., Hu, B., Good, V. M., Panaretou, B., Neckers, L., Clarke, P. A., Workman, P., et al. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.07.021 · Cited by 202 · see citing works
“The tyrosine kinase v-Src is a well-known Hsp90-Cdc37dependent client (Brugge, 1986; Xu and Lindquist, 1993), the activity of which in yeast is a widely used reporter for analysis of functionality in the Hsp90 chaperone system (Nathan and Lindquist, 1995; Panaretou et al.”
BackgroundMethodHeat shock protein 90 mediates macrophage activation by Taxol and bacterial lipopolysaccharide
Byrd, C. A., Bornmann, W. G., Erdjument‐Bromage, H., Tempst, P., Pavletich, N. P., Rosen, N. X., Nathan, C., & Ding, A. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5645 · Cited by 199 · see citing works
Stancato, L. F., Silverstein, A. M., Owens-Grillo, J. K., Chow, Y., Jove, R., & Pratt, W. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.7.4013 · Cited by 201 · see citing works
Hold 'em and Fold 'em: Chaperones and Signal Transduction
Bohen, S. P., Kralli, A., & Yamamoto, K. R. (1995) · Science · doi:10.1126/science.7761850 · Cited by 196 · see citing works
Hof, W. V. ’., & Resh, M. D. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.136.5.1023 · Cited by 187 · see citing works
“However, other studies imply that the pp50-pp90 complex functions to stabilize tyrosine kinase activity of the soluble form of v-Src (18, 55).”
BackgroundChandarlapaty, S., Sawai, A., Ye, Q., Scott, A., Silinski, M. A. R., Huang, K., Fadden, P., Partdrige, J., Hall, S. E., Steed, P. M., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1667 · Cited by 186 · see citing works
Xu, Y., Singer, M. A., & Lindquist, S. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.1.109 · Cited by 184 · see citing works
Self-citationChen, C., Chen, Y., Dai, K., Chen, P., Riley, D. J., & Lee, W. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4691 · Cited by 183 · see citing works
“Likewise, and for many of the same reasons, the mechanism by which hsp75 chaperones Rb will be a challenging issue to resolve, as it has been for other proteins (53, 55).”
BackgroundProtein Homeostasis and the Phenotypic Manifestation of Genetic Diversity: Principles and Mechanisms
Jarosz, D. F., Taipale, M., & Lindquist, S. (2010) · Annual Review of Genetics · doi:10.1146/annurev.genet.40.110405.090412 · Cited by 179 · see citing works
Self-citationOld and New Approaches to Target the Hsp90 Chaperone
Sanchez, J., Carter, T. R., Cohen, M. S., & Blagg, B. S. J. (2020) · Current Cancer Drug Targets · doi:10.2174/1568009619666191202101330 · Cited by 183 · see citing works
Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones*
Pratt, W. B., & Toft, D. O. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0303 · Cited by 1,791 · see citing works
The origins of cancer robustness and evolvability
Tian, T., Olson, S., Whitacre, J. M., & Harding, A. S. (2010) · Integrative Biology · doi:10.1039/c0ib00046a · Cited by 168 · see citing works
Mollapour, M., Tsutsumi, S., Truman, A. W., Xu, W., Vaughan, C. K., Beebe, K., Konstantinova, A., Vourganti, S., Panaretou, B., Piper, P. W., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.02.011 · Cited by 165 · see citing works
“…as previously described (Panaretou and Piper, 1996). v-Src, GR, Ste11DN, and Rlm1 Activation Assays Ste11DN induction was analyzed as previously described (Louvion et al., 1998). v-Src induction and activation were analyzed as previously described (Murphy et al., 1993; Xu and Lindquist, 1993).”
MethodThe Hsp90 complex—a super-chaperone machine as a novel drug target
Scheibel, T., & Büchner, J. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(98)00120-8 · Cited by 164 · see citing works
Dittmar, K. D., Banach, M., Galigniana, M. D., & Pratt, W. B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7358 · Cited by 163 · see citing works
Discovery and development of heat shock protein 90 inhibitors
Taldone, T., Sun, W., & Chiosis, G. (2008) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2008.10.087 · Cited by 162 · see citing works
Whitelaw, M. L., Gustafsson, J.-Α., & Poellinger, L. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8343 · Cited by 161 · see citing works
The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90
Wandinger, S. K., Suhre, M. H., Wegele, H., & Büchner, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600930 · Cited by 158 · see citing works
“their active state (Xu and Lindquist, 1993; Nathan and Lindquist, 1995; Nathan et al, 1997).”
BackgroundConservation of Hsp90 macromolecular complexes in Saccharomyces cerevisiae.
Chang, H.-C., & Lindquist, S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31486-2 · Cited by 158 · see citing works
Self-citationTumor Selectivity of Hsp90 Inhibitors: The Explanation Remains Elusive
Chiosis, G., & Neckers, L. (2006) · ACS Chemical Biology · doi:10.1021/cb600224w · Cited by 156 · see citing works
Molecular chaperones: The busy life of Hsp90
Mayer, M. P., & Bukau, B. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80203-6 · Cited by 156 · see citing works
“v-Src and c-Src require Hsp90 for maturation of their catalytic activity, and c-Src also needs Hsp90 in order to be a substrate for the regulatory kinase Csk [11,12].”
SBA1 Encodes a Yeast Hsp90 Cochaperone That Is Homologous to Vertebrate p23 Proteins
Fang, Y., Fliss, A., Rao, J., & Caplan, A. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3727 · Cited by 154 · see citing works
Inhibition of Hsp90: a new strategy for inhibiting protein kinases
Sreedhar, A. S., Sőti, C., & Csermely, P. (2003) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2003.11.027 · Cited by 148 · see citing works
“v-Src, c-Src [51] v-Fes, c-Fes, v-Fps, v-Ros, v-Yes Lck, v-Fgr, c-Fgr v-Abl, c-Abl [52,53] Wee1 [56,57] Sevenless c-Met [58] p75-v-erbA p185erbB2 [50] Insulin, ILGF, EGF, PDGF receptors”
BackgroundThe Plasticity of the Hsp90 Co-chaperone System
Sahasrabudhe, P., Rohrberg, J., Biebl, M. M., Rutz, D. A., & Buchner, J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.08.004 · Cited by 136 · see citing works
Duina, A. A., Kalton, H. M., & Gaber, R. F. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.30.18974 · Cited by 143 · see citing works
Duval, M., Bœuf, F. L., Huot, J., & Gratton, J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-05-0467 · Cited by 140 · see citing works
“Hsp90 is thought to direct the folding of Src kinases into the inactive conformation, which prevents their degradation (Xu and Lindquist, 1993; Xu et al., 1999).”
BackgroundHsp90 as a therapeutic target in prostate cancer
Solit, D. (2003) · Seminars in Oncology · doi:10.1016/s0093-7754(03)00346-4 · Cited by 140 · see citing works
The heat shock protein 83 (Hsp83) is required for Raf‐mediated signalling in Drosophila
van der Straten, A., Rommel, C., Dickson, B. J., & Hafen, E. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1961 · Cited by 140 · see citing works
“…Raf This spatial restriction can be overcome either by ectopicand casein kinase II (Miyata and Yahara, 1992; Stancato expression of Boss or by direct activation of Sev in theet al., 1993; Xu and Lindquist, 1993; Wartmann and Davis, cone cell precursors (Basler et al., 1991; Van Vactor et al.,1994).”
BackgroundHormone-dependent Transactivation by the Human Androgen Receptor Is Regulated by a dnaJ Protein
Caplan, A. J., Langley, E., Wilson, E. M., & Vidal, J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5251 · Cited by 139 · see citing works
Kunisawa, J., & Shastri, N. (2006) · Immunity · doi:10.1016/j.immuni.2006.03.015 · Cited by 138 · see citing works
Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis
Zhao, X. M., Chen, Z., Zhao, J. B., Zhang, P. P., Pu, Y. F., Jiang, S. H., Hou, J. J., Cui, Y. M., Jia, X. L., & Zhang, S. Q. (2016) · Cell Death & Disease · doi:10.1038/cddis.2015.390 · Cited by 135 · see citing works
“Hsp90 has been implicated in the stabilization of a number of kinases, including pp60v-src and Raf-1.(18,19) Loss of Hsp90 function results in their destabilization and rapid degradation by the ubiquitin–proteasome pathway.”
BackgroundThe Yeast Hsp110 Family Member, Sse1, Is an Hsp90 Cochaperone
Liu, X., Morano, K. A., & Thiele, D. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.38.26654 · Cited by 133 · see citing works
The Turn Motif Is a Phosphorylation Switch That Regulates the Binding of Hsp70 to Protein Kinase C
Gao, T., & Newton, A. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204335200 · Cited by 134 · see citing works
Morano, K. A., & Thiele, D. J. (1999) · Europe PMC (PubMed Central) · Cited by 134 · see citing works
Physical Interaction of Mammalian CDC37 with CDK4
Dai, K., Kobayashi, R., & Beach, D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.36.22030 · Cited by 134 · see citing works
- Authors
- Xu, Y., & Lindquist, S.
- Affiliations
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1993-08
- Volume
- 90
- Issue
- 15
- Pages
- 7074-7078
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC47078
- OpenAlex
- W2085643470
- Cited by
- 416
- References
- 33
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 10 · 2023: 7 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 10 · 2015: 5 · 2014: 14 · 2013: 5 · 2012: 12
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Chicago
- National Institutes of Health
- National Institute of General Medical Sciences (GM-25874)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- HSP90, pp60v-src, tyrosine kinase, kinase activation, protein stability, cell cycle arrest, tyrosine phosphorylation, oncogenic kinase, Src kinase, Saccharomyces cerevisiae, kinase specificity
- MeSH terms
- Cell Cycle, Chromosome Deletion, Genes, Fungal, Heat-Shock Proteins, Phosphoproteins, Recombinant Proteins, Saccharomyces cerevisiae, Tyrosine, Oncogene Protein pp60(v-src), Gene Expression, Mutagenesis, Insertional, Oncogene Proteins v-abl, Proto-Oncogene Proteins pp60(c-src), Phosphotyrosine
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