Distinct Roles of Phosphoinositide-3 Kinase and Phospholipase Cγ2 in B-Cell Receptor-Mediated Signal Transduction
Open accessAbstract
During B-cell receptor (BCR) signaling, phosphoinositide-3 kinase (PI3K) is thought to function upstream of phospholipase Cgamma2 (PLCgamma2). PLCgamma2 deficiency specifically impedes transitional type 2 (T2) to follicular (FO) mature B-cell transition. Here, we demonstrate that PI3K deficiency specifically impaired T2-to-FO mature B-cell transition and marginal zone B-cell development. Furthermore, we investigated the functional relationship between PI3K and PLCgamma2 using PI3K-/-, PLCgamma2-/-, and PI3K-/- PLCgamma2-/- B cells. Interestingly, PLCgamma2 deficiency had no effect on BCR-mediated PI3K activation, whereas PI3K deficiency only partially blocked activation of PLCgamma2. Moreover, whereas PI3K-/- PLCgamma2-/- double deficiency did not affect hematopoiesis, it resulted in embryonic lethality. PI3K-/- PLCgamma2-/- fetal liver cells transplanted into B-cell null JAK3-/- mice failed to restore development of peripheral B cells and failed to progress through early B-cell development at the pro-B- to pre-B-cell transition, a more severe phenotype than was observed with either PI3K or PLCgamma2 single-deficiency B cells. Consistent with this finding, BCR signaling was more severely impaired in the absence of both PI3K and PLCgamma2 genes than in the absence of either one alone. Taken together, these results demonstrate that whereas PI3K functions upstream of PLCgamma2, activation of PLCgamma2 can occur independently of PI3K and that PI3K and PLCgamma2 also have distinct functions in BCR signal transduction.
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PLCγ2-deficient and inducible PLCγ2−/− mice lack the ability to respond to antigens.
“Indeed, PLCγ2-deficient and inducible PLCγ2−/− mice have been widely shown to lack the ability to respond to antigens (24, 26, 27, 28).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [27]
The Abstract (page not provided) states that PLCγ2-deficient B cells are unable to respond to antigens. The paper does not establish the same claim for inducible PLCγ2−/− mice, so that part of the citing sentence is unsupported by our copy. (LLM, conf=0.85)
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Cites
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
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-citationCutting 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
Phospholipase 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 · cited 1× · see citing works
“Specifically, we found in the present and previous (18, 65) studies that even though PI3K and PLC 2 deficiency weakened BCR-induced Ca(2) flux to the same extent, deficiency of the p85 -p55 -p50 regulatory subunits of PI3K impaired FO, MZ, and B1 B-cell development, whereas we showed in previous studies (71, 74) that…”
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- [1]Alessi, D. R., M. Andjelkovic, B. Caudwell, P. Cron, N. Morrice, P. Cohen, and B. A. Hemmings. 1996. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15:6541-6551. [PMC free article] [PubMed] [Google Scholar]
- [2]Ansel, K. M., and J. G. Cyster. 2001. Chemokines in lymphopoiesis and lymphoid organ development. Curr. Opin. Immunol. 13:172-179. [DOI] [PubMed] [Google Scholar]
- [3]Blake, R. A., G. L. Schieven, and S. P. Watson. 1994. Collagen stimulates tyrosine phosphorylation of phospholipase C-gamma 2 but not phospholipase C-gamma 1 in human platelets. FEBS Lett. 353:212-216. [DOI] [PubMed] [Google Scholar]
- [4]Bonilla, F. A., R. M. Fujita, V. I. Pivniouk, A. C. Chan, and R. S. Geha. 2000. Adapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signaling via Fcγ receptors I and II/III. Proc. Natl. Acad. Sci. USA 97:1725-1730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5]Bourette, R. P., G. M. Myles, J. L. Choi, and L. R. Rohrschneider. 1997. Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-γ2 by the M-CSF receptor is necessary for differentiation signaling. EMBO J. 16:5880-5893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6]Burgering, B. M., and P. J. Coffer. 1995. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376:599-602. [DOI] [PubMed] [Google Scholar]
- [7]Cariappa, A., and S. Pillai. 2002. Antigen-dependent B-cell development. Curr. Opin. Immunol. 14:241-249. [DOI] [PubMed] [Google Scholar]
- [8]Cariappa, A., M. Tang, C. Parng, E. Nebelitskiy, M. Carroll, K. Georgopoulos, and S. Pillai. 2001. The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21. Immunity 14:603-615. [DOI] [PubMed] [Google Scholar]
- [9]Chantry, D., A. Vojtek, A. Kashishian, D. A. Holtzman, C. Wood, P. W. Gray, J. A. Cooper, and M. F. Hoekstra. 1997. p110δ, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J. Biol. Chem. 272:19236-19241. [DOI] [PubMed] [Google Scholar]
- [10]Clayton, E., G. Bardi, S. E. Bell, D. Chantry, C. P. Downes, A. Gray, L. A. Humphries, D. Rawlings, H. Reynolds, E. Vigorito, and M. Turner. 2002. A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation. J. Exp. Med. 196:753-763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11]Coggeshall, K. M., J. C. McHugh, and A. Altman. 1992. Predominant expression and activation-induced tyrosine phosphorylation of phospholipase C-γ2 in B lymphocytes. Proc. Natl. Acad. Sci. USA 89:5660-5664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12]Datta, S. R., A. Brunet, and M. E. Greenberg. 1999. Cellular survival: a play in three Akts. Genes Dev. 13:2905-2927. [DOI] [PubMed] [Google Scholar]
- [13]Dusi, S., M. Donini, V. Della Bianca, and F. Rossi. 1994. Tyrosine phosphorylation of phospholipase C-γ2 is involved in the activation of phosphoinositide hydrolysis by Fc receptors in human neutrophils. Biochem. Biophys. Res. Commun. 201:1100-1108. [DOI] [PubMed] [Google Scholar]
- [14]Falasca, M., S. K. Logan, V. P. Lehto, G. Baccante, M. A. Lemmon, and J. Schlessinger. 1998. Activation of phospholipase C gamma by PI 3-kinase-induced PH domain-mediated membrane targeting. EMBO J. 17:414-422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15]Franke, T. F., D. R. Kaplan, and L. C. Cantley. 1997. PI3K: downstream AKTion blocks apoptosis. Cell 88:435-437. [DOI] [PubMed] [Google Scholar]
- [16]Fruman, D. A. 2004. Phosphoinositide 3-kinase and its targets in B-cell and T-cell signaling. Curr. Opin. Immunol. 16:314-320. [DOI] [PubMed] [Google Scholar]
- [17]Fruman, D. A., F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, R. T. Bronson, C. R. Kahn, and L. C. Cantley. 2000. Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat. Genet. 26:379-382. [DOI] [PubMed] [Google Scholar]
- [18]Fruman, D. A., S. B. Snapper, C. M. Yballe, L. Davidson, J. Y. Yu, F. W. Alt, and L. C. Cantley. 1999. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α. Science 283:393-397. [DOI] [PubMed] [Google Scholar]
- [19]Fu, C., C. W. Turck, T. Kurosaki, and A. C. Chan. 1998. BLNK: a central linker protein in B cell activation. Immunity 9:93-103. [DOI] [PubMed] [Google Scholar]
- [20]Fukuda, M., T. Kojima, H. Kabayama, and K. Mikoshiba. 1996. Mutation of the pleckstrin homology domain of Bruton's tyrosine kinase in immunodeficiency impaired inositol 1,3,4,5-tetrakisphosphate binding capacity. J. Biol. Chem. 271:30303-30306. [DOI] [PubMed] [Google Scholar]
- [21]Gauld, S. B., J. M. Dal Porto, and J. C. Cambier. 2002. B cell antigen receptor signaling: roles in cell development and disease. Science 296:1641-1642. [DOI] [PubMed] [Google Scholar]
- [22]Girkontaite, I., K. Missy, V. Sakk, A. Harenberg, K. Tedford, T. Potzel, K. Pfeffer, and K. D. Fischer. 2001. Lsc is required for marginal zone B-cells, regulation of lymphocyte motility and immune responses. Nat. Immunol. 2:855-862. [DOI] [PubMed] [Google Scholar]
- [23]Gold, M. R., M. P. Scheid, L. Santos, M. Dang-Lawson, R. A. Roth, L. Matsuuchi, V. Duronio, and D. L. Krebs. 1894. The B cell antigen receptor activates the Akt (protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase. J. Immunol. 163:1894-1905. [PubMed] [Google Scholar]
- [24]Guinamard, R., M. Okigaki, J. Schlessinger, and J. V. Ravetch. 2000. Absence of marginal zone B-cells in Pyk-2-deficient mice defines their role in the humoral response. Nat. Immunol. 1:31-36. [DOI] [PubMed] [Google Scholar]
- [25]Hardy, R. R., and K. Hayakawa. 2001. B-cell development pathways. Annu. Rev. Immunol. 19:595-621. [DOI] [PubMed] [Google Scholar]
- [27]Healy, J. I., and C. C. Goodnow. 1998. Positive versus negative signaling by lymphocyte antigen receptors. Annu. Rev. Immunol. 16:645-670. [DOI] [PubMed] [Google Scholar]
- [28]Hemmings, B. A. 1997. Akt signaling: linking membrane events to life and death decisions. Science 275:628-630. [DOI] [PubMed] [Google Scholar]
- [29]Hombach, J., T. Tsubata, L. Leclercq, H. Stappert, and M. Reth. 1990. Molecular components of the B-cell antigen receptor complex of the IgM class. Nature 343:760-762. [DOI] [PubMed] [Google Scholar]
- [30]Ishiai, M., M. Kurosaki, R. Pappu, K. Okawa, I. Ronko, C. Fu, M. Shibata, A. Iwamatsu, A. C. Chan, and T. Kurosaki. 1999. BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. Immunity 10:117-125. [DOI] [PubMed] [Google Scholar]
- [31]Ishiai, M., H. Sugawara, M. Kurosaki, and T. Kurosaki. 1999. Cutting edge: association of phospholipase C-γ2 Src homology 2 domains with BLNK is critical for B cell antigen receptor signaling. J. Immunol. 163:1746-1749. [PubMed] [Google Scholar]
- [32]Jou, S. T., N. Carpino, Y. Takahashi, R. Piekorz, J. R. Chao, D. Wang, and J. N. Ihle. 2002. Essential, nonredundant role for the phosphoinositide 3-kinase p110δ in signaling by the B-cell receptor complex. Mol. Cell. Biol. 22:8580-8591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33]Jumaa, H., B. Wollscheid, M. Mitterer, J. Wienands, M. Reth, and P. J. Nielsen. 1999. Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65. Immunity 11:547-554. [DOI] [PubMed] [Google Scholar]
- [34]Karasuyama, H., A. Kudo, and F. Melchers. 1990. The proteins encoded by the VpreB and lambda 5 pre-B cell-specific genes can associate with each other and with mu heavy chain. J. Exp. Med. 172:969-972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35]Kiener, P. A., B. M. Rankin, A. L. Burkhardt, G. L. Schieven, L. K. Gilliland, R. B. Rowley, J. B. Bolen, and J. A. Ledbetter. 1993. Cross-linking of Fcγ receptor I (FcγRI) and receptor II (FcγRII) on monocytic cells activates a signal transduction pathway common to both Fc receptors that involves the stimulation of p72 Syk protein tyrosine kinase. J. Biol. Chem. 268:24442-24448. [PubMed] [Google Scholar]
- [36]Kitamura, D., J. Roes, R. Kuhn, and K. Rajewsky. 1991. A B-cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature 350:423-426. [DOI] [PubMed] [Google Scholar]
- [37]Koyasu, S. 2003. The role of PI3K in immune cells. Nat. Immunol. 4:313-319. [DOI] [PubMed] [Google Scholar]
- [38]Kurosaki, T. 1999. Genetic analysis of B cell antigen receptor signaling. Annu. Rev. Immunol. 17:555-592. [DOI] [PubMed] [Google Scholar]
- [39]Lam, K. P., R. Kuhn, and K. Rajewsky. 1997. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90:1073-1083. [DOI] [PubMed] [Google Scholar]
- [40]Leitges, M., C. Schmedt, R. Guinamard, J. Davoust, S. Schaal, S. Stabel, and A. Tarakhovsky. 1996. Immunodeficiency in protein kinase cβ-deficient mice. Science 273:788-791. [DOI] [PubMed] [Google Scholar]
- [41]Liao, F., H. S. Shin, and S. G. Rhee. 1993. Cross-linking of Fc gamma RIIIA on natural killer cells results in tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2. J. Immunol. 150:2668-2674. [PubMed] [Google Scholar]
- [42]Loder, F., B. Mutschler, R. J. Ray, C. J. Paige, P. Sideras, R. Torres, M. C. Lamers, and R. Carsetti. 1999. B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J. Exp. Med. 190:75-89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [43]Martin, F., and J. F. Kearney. 2001. B1 cells: similarities and differences with other B cell subsets. Curr. Opin. Immunol. 13:195-201. [DOI] [PubMed] [Google Scholar]
- [44]Martin, F., and J. F. Kearney. 2000. Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk. Immunity 12:39-49. [DOI] [PubMed] [Google Scholar]
- [45]Minegishi, Y., J. Rohrer, E. Coustan-Smith, H. M. Lederman, R. Pappu, D. Campana, A. C. Chan, and M. E. Conley. 1999. An essential role for BLNK in human B cell development. Science 286:1954-1957. [DOI] [PubMed] [Google Scholar]
- [46]Miura, O., N. Nakamura, J. N. Ihle, and N. Aoki. 1994. Erythropoietin-dependent association of phosphatidylinositol 3-kinase with tyrosine-phosphorylated erythropoietin receptor. J. Biol. Chem. 269:614-620. [PubMed] [Google Scholar]
- [47]Mombaerts, P., J. Iacomini, R. S. Johnson, K. Herrup, S. Tonegawa, and V. E. Papaioannou. 1992. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 68:869-877. [DOI] [PubMed] [Google Scholar]
- [48]Niiro, H., and E. A. Clark. 2002. Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2:945-956. [DOI] [PubMed] [Google Scholar]
- [49]Nosaka, T., J. M. van Deursen, R. A. Tripp, W. E. Thierfelder, B. A. Witthuhn, A. P. McMickle, P. C. Doherty, G. C. Grosveld, and J. N. Ihle. 1995. Defective lymphoid development in mice lacking Jak3. Science 270:800-802. [DOI] [PubMed] [Google Scholar]
- [50]Okkenhaug, K., A. Bilancio, G. Farjot, H. Priddle, S. Sancho, E. Peskett, W. Pearce, S. E. Meek, A. Salpekar, M. D. Waterfield, A. J. Smith, and B. Vanhaesebroeck. 2002. Impaired B and T cell antigen receptor signaling in p110δ PI 3-kinase mutant mice. Science 297:1031-1034. [DOI] [PubMed] [Google Scholar]
- [51]Okkenhaug, K., and B. Vanhaesebroeck. 2003. PI3K in lymphocyte development, differentiation and activation. Nat. Rev. Immunol. 3:317-330. [DOI] [PubMed] [Google Scholar]
- [52]Oliver, A. M., F. Martin, and J. F. Kearney. 1999. IgMhighCD21high lymphocytes enriched in the splenic marginal zone generate effector cells more rapidly than the bulk of follicular B cells. J. Immunol. 162:7198-7207. [PubMed] [Google Scholar]
- [53]Pappu, R., A. M. Cheng, B. Li, Q. Gong, C. Chiu, N. Griffin, M. White, B. P. Sleckman, and A. C. Chan. 1999. Requirement for B cell linker protein (BLNK) in B cell development. Science 286:1949-1954. [DOI] [PubMed] [Google Scholar]
- [54]Parganas, E., D. Wang, D. Stravopodis, D. J. Topham, J. C. Marine, S. Teglund, E. F. Vanin, S. Bodner, O. R. Colamonici, J. M. van Deursen, G. Grosveld, and J. N. Ihle. 1998. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93:385-395. [DOI] [PubMed] [Google Scholar]
- [55]Park, D. J., H. K. Min, and S. G. Rhee. 1992. Inhibition of CD3-linked phospholipase C by phorbol ester and by cAMP is associated with decreased phosphotyrosine and increased phosphoserine contents of PLC-gamma 1. J. Biol. Chem. 267:1496-1501. [PubMed] [Google Scholar]
- [56]Park, S. Y., K. Saijo, T. Takahashi, M. Osawa, H. Arase, N. Hirayama, K. Miyake, H. Nakauchi, T. Shirasawa, and T. Saito. 1995. Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. Immunity 3:771-782. [DOI] [PubMed] [Google Scholar]
- [57]Ren, C. L., T. Morio, S. M. Fu, and R. S. Geha. 1994. Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase Cγ2. J. Exp. Med. 179:673-680. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [58]Reth, M., J. Wienands, and W. W. Schamel. 2000. An unsolved problem of the clonal selection theory and the model of an oligomeric B-cell antigen receptor. Immunol. Rev. 176:10-18. [DOI] [PubMed] [Google Scholar]
- [60]Rhee, S. G., and K. D. Choi. 1992. Regulation of inositol phospholipid-specific phospholipase C isozymes. J. Biol. Chem. 267:12393-12396. [PubMed] [Google Scholar]
- [61]Salim, K., M. J. Bottomley, E. Querfurth, M. J. Zvelebil, I. Gout, R. Scaife, R. L. Margolis, R. Gigg, C. I. Smith, P. C. Driscoll, M. D. Waterfield, and G. Panayotou. 1996. Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase. EMBO J. 15:6241-6250. [PMC free article] [PubMed] [Google Scholar]
- [62]Schuler, W., I. J. Weiler, A. Schuler, R. A. Phillips, N. Rosenberg, T. W. Mak, J. F. Kearney, R. P. Perry, and M. J. Bosma. 1986. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell 46:963-972. [DOI] [PubMed] [Google Scholar]
- [63]Shinkai, Y., G. Rathbun, K. P. Lam, E. M. Oltz, V. Stewart, M. Mendelsohn, J. Charron, M. Datta, F. Young, A. M. Stall, et al. 1992. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68:855-867. [DOI] [PubMed] [Google Scholar]
- [64]Suzuki, H., S. Matsuda, Y. Terauchi, M. Fujiwara, T. Ohteki, T. Asano, T. W. Behrens, T. Kouro, K. Takatsu, T. Kadowaki, and S. Koyasu. 2003. PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction. Nat. Immunol. 4:280-286. [DOI] [PubMed] [Google Scholar]
- [65]Suzuki, H., Y. Terauchi, M. Fujiwara, S. Aizawa, Y. Yazaki, T. Kadowaki, and S. Koyasu. 1999. Xid-like immunodeficiency in mice with disruption of the p85α subunit of phosphoinositide 3-kinase. Science 283:390-392. [DOI] [PubMed] [Google Scholar]
- [66]Ting, A. T., C. J. Dick, R. A. Schoon, L. M. Karnitz, R. T. Abraham, and P. J. Leibson. 1995. Interaction between lck and syk family tyrosine kinases in Fc gamma receptor-initiated activation of natural killer cells. J. Biol. Chem. 270:16415-16421. [DOI] [PubMed] [Google Scholar]
- [67]Torres, R. M., H. Flaswinkel, M. Reth, and K. Rajewsky. 1996. Aberrant B cell development and immune response in mice with a compromised BCR complex. Science 272:1804-1808. [DOI] [PubMed] [Google Scholar]
- [68]Tsubata, T., and M. Reth. 1990. The products of pre-B-cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface. J. Exp. Med. 172:973-976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [69]Vanhaesebroeck, B., M. J. Welham, K. Kotani, R. Stein, P. H. Warne, M. J. Zvelebil, K. Higashi, S. Volinia, J. Downward, and M. D. Waterfield. 1997. P110δ, a novel phosphoinositide 3-kinase in leukocytes. Proc. Natl. Acad. Sci. USA 94:4330-4335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [70]Wahl, M. I., T. O. Daniel, and G. Carpenter. 1988. Antiphosphotyrosine recovery of phospholipase C activity after EGF treatment of A-431 cells. Science 241:968-970. [DOI] [PubMed] [Google Scholar]
- [72]Wang, D., D. Stravopodis, S. Teglund, J. Kitazawa, and J. N. Ihle. 1996. Naturally occurring dominant negative variants of Stat5. Mol. Cell. Biol. 16:6141-6148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [73]Weiss, A., G. Koretzky, R. C. Schatzman, and T. Kadlecek. 1991. Functional activation of the T-cell antigen receptor induces tyrosine phosphorylation of phospholipase C-γ1. Proc. Natl. Acad. Sci. USA 88:5484-5488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [75]Wienands, J., J. Schweikert, B. Wollscheid, H. Jumaa, P. J. Nielsen, and M. Reth. 1998. SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J. Exp. Med. 188:791-795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [76]Xu, X., and A. S. Chong. 1996. Vav in natural killer cells is tyrosine phosphorylated upon cross-linking of Fc gamma RIIIA and is constitutively associated with a serine/threonine kinase. Biochem. J. 318:527-532. [DOI] [PMC free article] [PubMed] [Google Scholar]
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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
- Authors
- Dai, X., Chen, Y., Schuman, J., Hua, Z., Adamson, J. W., Wen, R., & Wang, D.
- Affiliations
- Versiti Blood Center of Wisconsin (US)
- State Key Laboratory of Pharmaceutical Biotechnology (CN)
- Medical College of Wisconsin (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-01-01
- Volume
- 26
- Issue
- 1
- Pages
- 88-99
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1317611
- OpenAlex
- W2122959084
- Cited by
- 13
- References
- 4
- Citations by year
- 2024: 1 · 2021: 1 · 2017: 1 · 2016: 1 · 2013: 1 · 2012: 1
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL073284)
- National Institute of Allergy and Infectious Diseases (R01AI052327, R01 AI52327)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- phosphatidylinositol 3-kinase, PLCγ2, B cell receptor signaling, B cell development, marginal zone B cells, embryonic lethality, signal transduction
- MeSH terms
- Animals, B-Lymphocytes, Cell Differentiation, Embryo, Mammalian, Enzyme Activation, Lymphocyte Activation, Mice, Mutant Strains, Receptors, Antigen, B-Cell, Signal Transduction, Gene Deletion, Phosphatidylinositol 3-Kinases, Embryonic Development, Mice, Phospholipase C gamma
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 ›
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