Phospholipase Cγ2 Mediates RANKL-stimulated Lymph Node Organogenesis and Osteoclastogenesis
Open accessAbstract
Phospholipase Cgamma2 (PLCgamma2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCgamma2-deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-kappaB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCgamma2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCgamma2 markedly diminished RANKL-induced activation of NF-kappaB, AP-1, and NFATc1. Moreover, PLCgamma2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCgamma2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCgamma2 but not PLCgamma1 restores RANKL-mediated osteoclast differentiation of PLCgamma2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCgamma2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Blocking PLCγ2 impedes the early development and function of osteoclasts, thereby preventing bone loss in arthritis.
“Moreover, PLCγ2-deficient mouse studies showed that blocking PLCγ2 impedes the early development and function of osteoclasts, thereby preventing bone loss in arthritis (99, 100).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [100]
The osteoclast-formation results (page unavailable) show that PLCγ2-deficient bone marrow precursors failed to form multinucleated osteoclasts after RANKL stimulation. The in-vivo bone results report fewer osteoclasts and greater bone density in deficient mice. The paper does not show that PLCγ2 blockade prevents bone loss in arthritis, and it does not directly test mature osteoclast function. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights
Baldwin, A. S. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.649 · Cited by 5,882 · see citing works
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439 · see citing works
NF-κB AND REL PROTEINS: Evolutionarily Conserved Mediators of Immune Responses
Ghosh, S., May, M. J., & Kopp, E. B. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.225 · Cited by 5,182 · see citing works
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,015 · see citing works
Phosphorylation meets ubiquitination: the control of NF-κB activity
Karin, M., & Ben-Neriah, Y. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.621 · Cited by 4,766 · see citing works
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224 · see citing works
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351 · see citing works
Dérijard, B., Hibi, M., Wu, I.-H., Barrett, T., Su, B., Deng, T., Karin, M., & Davis, R. J. (1994) · Cell · doi:10.1016/0092-8674(94)90380-8 · Cited by 3,188 · see citing works
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701 · see citing works
TRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and Function
Rao, A., Luo, C. H., & Hogan, P. G. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.707 · Cited by 2,605 · see citing works
The stress-activated protein kinase subfamily of c-Jun kinases
Kyriakis, J. M., Banerjee, P. T., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., & Woodgett, J. R. (1994) · Nature · doi:10.1038/369156a0 · Cited by 2,601 · see citing works
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290 · see citing works
Hibi, M., Lin, A., Smeal, T., Minden, A., & Karin, M. (1993) · Genes & Development · doi:10.1101/gad.7.11.2135 · Cited by 1,886 · see citing works
Boulton, T. G., Nye, S. H., Robbins, D. J., Ip, N. Y., Radzlejewska, E., Morgenbesser, S. D., DePinho, R. A., Panayotatos, N., Cobb, M. H., & Yancopoulos, G. D. (1991) · Cell · doi:10.1016/0092-8674(91)90098-j · Cited by 1,876 · see citing works
Yoshida, H., Hayashi, S.-I., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L. D., & Nishikawa, S.-I. (1990) · Nature · doi:10.1038/345442a0 · Cited by 1,789 · see citing works
RANK is essential for osteoclast and lymph node development.
Dougall, W. C., Glaccum, M., Charrier, K., Rohrbach, K., Brasel, K., De Smedt, T., Daro, E., Smith, J., Tometsko, M. E., Maliszewski, C. R., et al. (1999) · Genes & Development · doi:10.1101/gad.13.18.2412 · Cited by 1,478 · see citing works
A chemokine-driven positive feedback loop organizes lymphoid follicles
Ansel, K. M., Ngo, V. N., Hyman, P. L., Luther, S. A., Förster, R., Sedgwick, J. D., Browning, J. L., Lipp, M., & Cyster, J. G. (2000) · Nature · doi:10.1038/35018581 · Cited by 1,282 · see citing works
c-Fos: a Key Regulator of Osteoclast-Macrophage Lineage Determination and Bone Remodeling
Grigoriadis, A. E., Wang, Z., Cecchini, M. G., Hofstetter, W., Felix, R., Fleisch, H. A., & Wagner, E. F. (1994) · Science · doi:10.1126/science.7939685 · Cited by 1,260 · see citing works
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signalingPreprint
Lomaga, M. A., Yeh, W., Sarosi, I., Duncan, G. S., Furlonger, C. L., Ho, A. P., Morony, S., Capparelli, C., Van, G. Y., Kaufman, S., et al. (1999) · Genes & Development · doi:10.1101/gad.13.8.1015 · Cited by 1,253 · see citing works
Pasparakis, M., Alexopoulou, L., Episkopou, V., & Kollias, G. A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1397 · Cited by 1,160 · see citing works
Förster, R., Mattis, A. E., Kremmer, E., Wolf, E., Brem, G., & Lipp, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81798-5 · Cited by 1,129 · see citing works
Requirement for NF-κB in osteoclast and B-cell development
Franzoso, G., Carlson, L., Xing, L., Poljak, L., Shores, E. W., Brown, K. D., Leonardi, A., Tran, T., Boyce, B. F., & Siebenlist, U. (1997) · Genes & Development · doi:10.1101/gad.11.24.3482 · Cited by 996 · see citing works
Abnormal Development of Peripheral Lymphoid Organs in Mice Deficient in Lymphotoxin
Togni, P. D., Goellner, J. J., Ruddle, N. H., Streeter, P. R., Andrea, F., Mariathasan, S., Smith, S. C., Carlson, R., Shornick, L. P., Strauss‐Schoenberger, J., et al. (1994) · Science · doi:10.1126/science.8171322 · Cited by 987 · see citing works
The Primary Structure of MEK, a Protein Kinase that Phosphorylates the ERK Gene Product
Crews, C. M., Alessandrini, A., & Erikson, R. L. (1992) · Science · doi:10.1126/science.1411546 · Cited by 930 · see citing works
The Lymphotoxin-β Receptor Induces Different Patterns of Gene Expression via Two NF-κB Pathways
Dejardin, E., Droin, N. M., Delhase, M., Haas, E., Cao, Y., Makris, C., Li, Z., Karin, M., Ware, C. F., & Green, D. R. (2002) · Immunity · doi:10.1016/s1074-7613(02)00423-5 · Cited by 923 · see citing works
Regulation of Phosphoinositide-specific Phospholipase C Isozymes
Rhee, S. G., & Bae, Y. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.24.15045 · Cited by 876 · see citing works
Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis
Koga, T., Inui, M., Inoue, K., Kim, S., Suematsu, A., Kobayashi, E., Iwata, T., Ohnishi, H., Matozaki, T., Kodama, T., et al. (2004) · Nature · doi:10.1038/nature02444 · Cited by 828 · see citing works
Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts.
McHugh, K. P., Hodivala-Dilke, K., Zheng, M., Namba, N., Lam, J. D., Novack, D., Feng, X., Ross, F., Hynes, R. O., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8905 · Cited by 786 · see citing works
Self-citationLymphoid organ development: from ontogeny to neogenesis
Drayton, D. L., Liao, S., Mounzer, R. H., & Ruddle, N. H. (2006) · Nature Immunology · doi:10.1038/ni1330 · Cited by 777 · see citing works
Regulation of inositol phospholipid-specific phospholipase C isozymes.
Rhee, S. G., & Choi, K. D. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42284-3 · Cited by 741 · see citing works
Increase of the Catalytic Activity of Phospholipase C-γ1 by Tyrosine Phosphorylation
Nishibe, S., Wahl, M. I., Hernández‐Sotomayor, S. M. T., Tonks, N. K., Rhee, S. G., & Carpenter, G. F. (1990) · Science · doi:10.1126/science.1700866 · Cited by 635 · see citing works
Koni, P. A., Sacca, R. E., Lawton, P., Browning, J. L., Ruddle, N. H., & Flavell, R. A. (1997) · Immunity · doi:10.1016/s1074-7613(00)80292-7 · Cited by 589 · see citing works
Nuclear Factor of Activated T-cells (NFAT) Rescues Osteoclastogenesis in Precursors Lacking c-Fos
Matsuo, K., Galson, D. L., Chen, Z., Peng, L., Laplace, C., Wang, K. Z. Q., Bachler, M. A., Amano, H., Aburatani, H., Ishikawa, H., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313973200 · Cited by 569 · see citing works
Phospholipase Cγ2 Is Essential in the Functions of B Cell and Several Fc Receptors
Wang, D., Feng, J., Wen, R., Marine, J.-C., Sangster, M. Y., Parganas, E., Hoffmeyer, A., Jackson, C. W., Cleveland, J. L., Murray, P. J., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00005-4 · Cited by 475 · see citing works
Self-citationThe TRAF Family of Signal Transducers Mediates NF-κB Activation by the TRANCE Receptor
Wong, B. R., Josien, R., Lee, S. Y., Vologodskaia, M., Steinman, R. M., & Choi, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.43.28355 · Cited by 458 · see citing works
Banks, T. A., Rouse, B. T., Kerley, M. K., Blair, P. J., Godfrey, V., Kuklin, N. A., Bouley, D. M., Thomas, J., Kanangat, S., & Mucenski, M. L. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.4.1685 · Cited by 440 · see citing works
Mócsai, A., Humphrey, M., Ziffle, J. V. V., Hu, Y., Burghardt, A., Spusta, S. C., Majumdar, S., Lanier, L., Lowell, C., & Nakamura, M. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401602101 · Cited by 436 · see citing works
Matsumoto, M., Kogawa, M., Wada, S., Takayanagi, H., Tsujimoto, M., Katayama, S., Hisatake, K., & Nogi, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408795200 · Cited by 436 · see citing works
CARMA1, BCL-10 and MALT1 in lymphocyte development and activation
Thome, M. (2004) · Nature Reviews Immunology · doi:10.1038/nri1352 · Cited by 391 · see citing works
Role of Lymphotoxin and the Type I TNF Receptor in the Formation of Germinal Centers
Matsumoto, M., Mariathasan, S., Nahm, M. H., Baranyay, F., Peschon, J. J., & Chaplin, D. (1996) · Science · doi:10.1126/science.271.5253.1289 · Cited by 374 · see citing works
Abnormal development of secondary lymphoid tissues in lymphotoxin β-deficient mice
Alimzhanov, M. B., Kuprash, D. V., Kosco‐Vilbois, M. H., Luz, A., Turetskaya, R. L., Tarakhovsky, A., Rajewsky, K., Nedospasov, S. A., & Pfeffer, K. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9302 · Cited by 370 · see citing works
Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice
Kaifu, T., Nakahara, J., Inui, M., Mishima, K., Momiyama, T., Kaji, M., Sugahara, A., Koito, H., Ujike, A., Nakamura, A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16923 · Cited by 342 · see citing works
Weiss, A., Koretzky, G. A., Schatzman, R. C., & Kadlecek, T. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5484 · Cited by 341 · see citing works
Fosl1 is a transcriptional target of c-Fos during osteoclast differentiation
Matsuo, K., Owens, J., Tonko, M., Elliott, C., Chambers, T. J., & Wagner, E. F. (2000) · Nature Genetics · doi:10.1038/72855 · Cited by 341 · see citing works
David, J., Sabapathy, K., Hoffmann, O., Idarraga, M. H., & Wagner, E. F. (2002) · Journal of Cell Science · doi:10.1242/jcs.00082 · Cited by 334 · see citing works
Miyawaki, S., Nakamura, Y., Suzuka, H., Koba, M., Shibata, Y., Yasumizu, R., & Ikehara, S. (1994) · European Journal of Immunology · doi:10.1002/eji.1830240224 · Cited by 330 · see citing works
Lee, S. E., Woo, K. M., Kim, S.-Y., Kim, H., Kwack, K., Lee, Z. H., & Kim, H.-H. (2002) · Bone · doi:10.1016/s8756-3282(01)00657-3 · Cited by 309 · see citing works
Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases
Salvador, J. M., Mittelstadt, P. R., Guszczynski, T., Copeland, T. D., Yamaguchi, H., Appella, E., Fornace, A. J., & Ashwell, J. D. (2005) · Nature Immunology · doi:10.1038/ni1177 · Cited by 306 · see citing works
Signal Transduction during Natural Killer Cell Activation: Inside the Mind of a Killer
Leibson, P. J. (1997) · Immunity · doi:10.1016/s1074-7613(00)80441-0 · Cited by 295 · see citing works
Nagy, T. R., & Clair, A. (2000) · Obesity Research · doi:10.1038/oby.2000.47 · Cited by 293 · see citing works
Li, X., Udagawa, N., Itoh, K., Suda, K., Murase, Y., Nishihara, T., Suda, T., & Takahashi, N. (2002) · Endocrinology · doi:10.1210/endo.143.8.8954 · Cited by 288 · see citing works
Ji, Q.-S., Winnier, G. E., Niswender, K. D., Horstman, D. A., Wisdom, R., Magnuson, M. A., & Carpenter, G. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.2999 · Cited by 270 · see citing works
PLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2
Mao, D., Epple, H., Uthgenannt, B., Novack, D. V., & Faccio, R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28775 · Cited by 214 · see citing works
Signal transduction from the B cell antigen-receptor
Campbell, K. S. (1999) · Current Opinion in Immunology · doi:10.1016/s0952-7915(99)80042-9 · Cited by 211 · see citing works
Natural killer cell activation in mice and men: different triggers for similar weapons?
Colucci, F., Santo, J. P. D., & Leibson, P. J. (2002) · Nature Immunology · doi:10.1038/ni0902-807 · Cited by 206 · see citing works
Matsushima, A., Kaisho, T., Rennert, P. D., Nakano, H., Kurosawa, K., Uchida, D., Takeda, K., Akira, S., & Matsumoto, M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.5.631 · Cited by 200 · see citing works
Hashimoto, A., Okada, H., Jiang, A., Kurosaki, M., Greenberg, S., Clark, E. A., & Kurosaki, T. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.7.1287 · Cited by 199 · see citing works
IL-4 abrogates osteoclastogenesis through STAT6-dependent inhibition of NF-κB
Abu‐Amer, Y. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10530 · Cited by 189 · see citing works
Hirasawa, N., Santini, F., & Beaven, M. A. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.10.5391 · Cited by 170 · see citing works
Jiang, A., Craxton, A., Kurosaki, T., & Clark, E. A. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.7.1297 · Cited by 170 · see citing works
Signaling crosstalk between RANKL and interferons in osteoclast differentiation.
Takayanagi, H., Kim, S., & Taniguchi, T. (2002) · Arthritis Research · doi:10.1186/ar581 · Cited by 166 · see citing works
Cutting Edge: Essential Role of Phospholipase C-γ2 in B Cell Development and Function
Hashimoto, A., Takeda, K., Inaba, M., Sekimata, M., Kaisho, T., Ikehara, S., Homma, Y., Akira, S., & Kurosaki, T. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.4.1738 · Cited by 155 · see citing works
Watanabe, D., Hashimoto, S., Ishiai, M., Matsushita, M., Baba, Y., Kishimoto, T., Kurosaki, T., & Tsukada, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103675200 · Cited by 136 · see citing works
v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation
Akagi, T., Shishido, T., Murata, K., & Hanafusa, H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.140210297 · Cited by 135 · see citing works
Bunting, K. D., Sangster, M. Y., Ihle, J. N., & Sorrentino, B. P. (1998) · Nature Medicine · doi:10.1038/nm0198-058 · Cited by 134 · see citing works
A Glanzmann’s mutation in β3 integrin specifically impairs osteoclast function
Feng, X., Novack, D. V., Faccio, R., Ory, D. S., Aya, K., Boyer, M. I., McHugh, K. P., Ross, F. P., & Teitelbaum, S. L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12040 · Cited by 134 · see citing works
Self-citationChao, T. S., Foster, D. A., Rapp, U. R., & Rosner, M. R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37289-7 · Cited by 128 · see citing works
Identification of Shp-2 as a Stat5A Phosphatase
Chen, Y., Wen, R., Yang, S., Schuman, J., Zhang, E. E., Yi, T., Feng, G., & Wang, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210572200 · Cited by 124 · see citing works
Self-citationThe Signaling Adapter Protein DAP12 Regulates Multinucleation During Osteoclast Development
Humphrey, M. B., Ogasawara, K., Yao, W., Spusta, S. C., Daws, M. R., Lane, N. E., Lanier, L. L., & Nakamura, M. C. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301234 · Cited by 123 · see citing works
Receptor Activator of Nuclear Factor-κB Ligand Activates Nuclear Factor-κB in Osteoclast Precursors*
Shi, W., Teitelbaum, S. L., Wang, M. W.-H., & Ross, F. P. (2001) · Endocrinology · doi:10.1210/endo.142.3.8031 · Cited by 122 · see citing works
Phospholipase C-γ2 Is a Critical Signaling Mediator for Murine NK Cell Activating Receptors
Tassi, I., Presti, R., Kim, S., Yokoyama, W. M., Gilfillan, S., & Colonna, M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.2.749 · Cited by 121 · see citing works
The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling
Lin, X., & Wang, D. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.08.022 · Cited by 121 · see citing works
Self-citationKawakami, Y., Hartman, S. E., Holland, P. M., Cooper, J. A., & Kawakami, T. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.4.1795 · Cited by 107 · see citing works
Roa, M., Paumet, F., Mao, J., David, B., & Blank, U. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.6.2815 · Cited by 107 · see citing works
Chen, Y., Kelm, R. J., Budd, R. C., Sobel, B. E., & Schneider, D. J. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20058 · Cited by 91 · see citing works
Self-citationTyrosine Residues in Phospholipase Cγ2 Essential for the Enzyme Function in B-cell Signaling
Rodriguez, R., Matsuda, M., Perišić, O., Bravo, J., Paul, A., Jones, N. P., Light, Y., Swann, K., Williams, R. L., & Katan, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107577200 · Cited by 90 · see citing works
Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR
Wen, R., Jou, S.-T., Chen, Y., Hoffmeyer, A., & Wang, D. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.12.6743 · Cited by 71 · see citing works
Self-citationConcerted action of the chemokine and lymphotoxin system in secondary lymphoid-organ development
Müller, G., & Lipp, M. (2003) · Current Opinion in Immunology · doi:10.1016/s0952-7915(03)00014-1 · Cited by 63 · see citing works
Jak3 Selectively Regulates Bax and Bcl-2 Expression To Promote T-Cell Development
Wen, R., Wang, D., McKay, C., Bunting, K. D., Marine, J., Vanin, E. F., Zambetti, G. P., Korsmeyer, S. J., Ihle, J. N., & Cleveland, J. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.2.678-689.2001 · Cited by 61 · see citing works
Self-citationReceptor Activator of Nuclear Factor- B Ligand Activates Nuclear Factor- B in Osteoclast Precursors
Wei, S. (2001) · Endocrinology · doi:10.1210/en.142.3.1290 · Cited by 57 · see citing works
Regunathan, J., Chen, Y., Kutleša, S., Dai, X., Bai, L., Wen, R., Wang, D., & Malarkannan, S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.8.5365 · Cited by 49 · see citing works
Self-citationFeng, X., Takeshita, S., Namba, N., Wei, S., Teitelbaum, S., & Ross, F. (2002) · Endocrinology · doi:10.1210/en.2002-220467 · Cited by 43 · see citing works
Self-citationPhospholipase Cγ2 Provides Survival Signals via Bcl2 and A1 in Different Subpopulations of B Cells
Wen, R., Chen, Y., Xue, L., Schuman, J., Yang, S., Morris, S. W., & Wang, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307318200 · Cited by 41 · see citing works
Self-citationAn important role of phospholipase Cγ1 in pre‐B‐cell development and allelic exclusion
Wen, R., Chen, Y., Schuman, J., Fu, G., Yang, S., Zhang, W., Newman, D. K., & Wang, D. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600405 · Cited by 39 · see citing works
Self-citationZhang, C., Hirasawa, N., & Beaven, M. A. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.10.4968 · Cited by 38 · see citing works
A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32).
Kawakami (1998) · International Journal of Hematology · doi:10.1016/s0925-5710(97)00109-6 · Cited by 11 · see citing works
Nutrition support in patients with multiple organ failure.
Campbell, I. T. (1998) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-199803000-00012 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mo- chizuki, S., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., Tsuda, E., Morinaga, T., Higashio, K., Udagawa, N., Takahashi, N., and Suda, T. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 3597-3602
- Mocsai, A., Humphrey, M. B., Van Ziffle, J. A., Hu, Y., Burghardt, A., Spusta, S. C., Majumdar, S., Lanier, L. L., Lowell, C. A., and Nakamura, M. C. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 6158 -6163
- Alimzhanov, M. B., Kuprash, D. V., Kosco-Vilbois, M. H., Luz, A., Turetskaya, R. L., Tarakhovsky, A., Rajewsky, K., Nedospasov, S. A., and Pfeffer, K. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 9302-9307
- Weiss, A., Koretzky, G., Schatzman, R. C., and Kadlecek, T. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 5484 -5488
- Akagi, T., Shishido, T., Murata, K., and Hanafusa, H. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 7290 -7295
- Ji, Q. S., Winnier, G. E., Niswender, K. D., Horstman, D., Wisdom, R., Magnuson, M. A., and Carpenter, G. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 2999 -3003
Cited by
Sorted by citations
Smooth Muscle Cell–Specific Runx2 Deficiency Inhibits Vascular Calcification
Sun, Y., Byon, C. H., Yuan, K., Chen, J., Mao, X., Heath, J. M., Javed, A., Zhang, K., Anderson, P. G., & Chen, Y. (2012) · Circulation Research · doi:10.1161/circresaha.112.267237 · Cited by 344 · see citing works
Self-citationIrie, N., Takada, Y., Watanabe, Y., Matsuzaki, Y., Naruse, C., Asano, M., Iwakura, Y., Suda, T., & Matsuo, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807598200 · Cited by 175 · see citing works
Regulation and physiological functions of mammalian phospholipase C
Nakamura, Y., & Fukami, K. (2017) · Journal of Biochemistry · doi:10.1093/jb/mvw094 · Cited by 122 · see citing works
Jakus, Z., Simon, E., Frommhold, D., Sperandio, M., & Mócsai, A. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081859 · Cited by 119 · see citing works
The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration
Jackson, J. T., Mulazzani, E., Nutt, S. L., & Masters, S. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100905 · Cited by 113 · see citing works
“While PLCγ1 plays a greater role in T cells, PLCγ2 is still important in terms of TCR signaling and the calpaincalpastatin system and when combined with PLCγ1 deletion.”
BackgroundInfluentialOsteoclast Signal Transduction During Bone Metastasis Formation
Győri, D., & Mócsai, A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00507 · Cited by 104 · see citing works
Cao, Q., Zhang, J., Liu, H., Wu, Q., Chen, J., & Chen, G. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.06.020 · Cited by 84 · see citing works
Mebarek, S., Abousalham, A., Magne, D., Do, L.-D., Bandorowicz‐Pikuła, J., Pikuła, S., & Buchet, R. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14035036 · Cited by 69 · see citing works
Receptor activator of nuclear factor-κB ligand is a novel inducer of myocardial inflammation
Ock, S., Ahn, J., Lee, S. H., Park, H., Son, J. W., Oh, J. G., Yang, D. K., Lee, W. S., Kim, H.-S., Rho, J., et al. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs078 · Cited by 59 · see citing works
RANKL/RANK – From bone physiology to breast cancer
Sigl, V., & Penninger, J. M. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.01.002 · Cited by 57 · see citing works
Serum response factor regulates bone formation via IGF-1 and Runx2 signals
Chen, J., Yuan, K., Mao, X., Miano, J. M., Wu, H., & Chen, Y. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1607 · Cited by 51 · see citing works
Self-citationActivation Mechanisms and Diverse Functions of Mammalian Phospholipase C
Kanemaru, K., & Nakamura, Y. (2023) · Biomolecules · doi:10.3390/biom13060915 · Cited by 51 · see citing works
Roles of Phospholipase C Isozymes in Organogenesis and Embryonic Development
Nakamura, Y., & Fukami, K. (2009) · Physiology · doi:10.1152/physiol.00031.2009 · Cited by 36 · see citing works
Khalmuratova, R., Shin, H., Kim, D. W., & Park, J. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.07.035 · Cited by 35 · see citing works
Phospholipase Cγ2 is required for basal but not oestrogen deficiency–induced bone resorption
Kertész, Z., Győri, D., Körmendi, S., Fekete, T., Kis‐Tóth, K., Jakus, Z., Schett, G. A., Rajnavölgyi, É., Dobó‐Nagy, C., & Mócsai, A. (2011) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2011.02556.x · Cited by 33 · see citing works
Bone Involvement in Rheumatoid Arthritis and Spondyloartritis: An Updated Review
Orsini, F., Crotti, C., Cincinelli, G., Taranto, R. D., Amati, A., Ferrito, M., VARENNA, M., & Caporali, R. F. (2023) · Biology · doi:10.3390/biology12101320 · Cited by 30 · see citing works
Chen, J., Sun, Y. J., Mao, X., Liu, Q., Wu, H., & Chen, Y. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.157743 · Cited by 30 · see citing works
Self-citationCsete, D., Simon, E., Alatshan, A., Aradi, P., Dobó‐Nagy, C., Jakus, Z., Benkő, S., Győri, D., & Mócsai, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00937 · Cited by 30 · see citing works
The roles of Orai and Stim in bone health and disease
Robinson, L. J., Blair, H. C., Barnett, J. B., & Soboloff, J. (2019) · Cell Calcium · doi:10.1016/j.ceca.2019.06.001 · Cited by 24 · see citing works
Yang, Z., Kim, S., Mahajan, S., Zamani, A., & Faccio, R. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.764928 · Cited by 17 · see citing works
Phospholipase Cγ2 Is Essential for Experimental Models of Epidermolysis Bullosa Acquisita
Szilveszter, K. P., Vikár, S., Horváth, Á. I., Helyes, Z., Sárdy, M., & Mócsai, A. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.09.019 · Cited by 10 · see citing works
Futosi, K., Kása, O., Szilveszter, K. P., & Mócsai, A. (2021) · Arthritis & Rheumatology · doi:10.1002/art.41704 · Cited by 10 · see citing works
MiR-9-1 controls osteoblastic regulation of lymphopoiesis
Zhang, Y., Lin, D., Zheng, Y., Chen, Y., Yu, M., Cui, D., Huang, M., Su, X., Sun, Y., Chen, Y., et al. (2023) · Leukemia · doi:10.1038/s41375-023-02014-8 · Cited by 7 · see citing works
Self-citationBone and Cartilage from Stem Cells: Growth Optimalization and Stabilization of Cell Phenotypes
O, J., Janne, E., Tommy, A., Rune, B., Engebretsen, L., Stale, P., Duroux-Richard, I., Jørgensen, C., & Jan, E. (2011) · InTech eBooks · doi:10.5772/19826 · Cited by 5 · see citing works
Decreased SH3BP2 inhibits osteoclast differentiation and function
Kawamoto, T., Fan, C., Gaivin, R. J., Levine, M. A., & Lietman, S. A. (2011) · Journal of Orthopaedic Research® · doi:10.1002/jor.21408 · Cited by 4 · see citing works
Nucleosides accelerate inflammatory osteolysis, acting as distinct innate immune activators
Pan, G., Zheng, R., Yang, P., Li, Y., Clancy, J. P., Liu, J., Feng, X., Garber, D. A., Spearman, P. W., & McDonald, J. M. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.400 · Cited by 4 · see citing works
Self-citationRANK and RANKL of Bones, T Cells, and the Mammary Glands
Sigl, V., & Penninger, J. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800571-2.00008-6 · Cited by 1 · see citing works
- Authors
- Chen, Y., Wang, X., Di, L., Fu, G., Chen, Y., Bai, L., Liu, J., Feng, X., McDonald, J. M., Michalek, S., He, Y., Yu, M., Fu, Y.-X., Wen, R., Wu, H., & Wang, D.
- Affiliations
- University of Alabama at Birmingham (US)
- Versiti Blood Center of Wisconsin (US)
- University of Chicago (US)
- Corresponding author
- Wu, Hui
- Wang, Demin
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 283
- Issue
- 43
- Pages
- 29593-29601
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2570883
- OpenAlex
- W1986056008
- Cited by
- 27
- References
- 84
- Citations by year
- 2023: 3 · 2021: 3 · 2020: 1 · 2019: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- University of Alabama at Birmingham
- University of Alabama
- National Institutes of Health (P30-AR46031, AR046031)
- National Heart, Lung, and Blood Institute (HL073284, R01HL073284)
- National Institute of Allergy and Infectious Diseases (R01AI079087, R01AI052327, AI079087, AI52327)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR046031, R03AR055339, AR046031-080003, AR055339, P30 AR 46031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- PLCγ2, RANKL, osteoclastogenesis, RANK signaling, NF-κB activation, MAPK signaling, p38 MAPK, JNK, NFATc1, AP-1, bone marrow-derived macrophages, monocyte-to-macrophage differentiation, PLCγ1, Peyer's patches
- MeSH terms
- Animals, Cell Differentiation, Lymph Nodes, Mice, Transgenic, Models, Biological, Osteoclasts, Spleen, Signal Transduction, Cytokines, Organogenesis, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases, Mice, Phospholipase C gamma, RANK Ligand
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
