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J Exp Med. 1996 February 1; 183(2): 547–560.
PMCID: PMC2192439

CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-gamma(1) upon B cell activation


Cross-linking B cell antigen receptor (BCR) elicits early signal transduction events, including activation of protein tyrosine kinases, phosphorylation of receptor components, activation of phospholipase C- gamma (PLC-gamma), and increases in intracellular free Ca2+. In this article, we report that cross-linking the BCR led to a rapid translocation of cytosolic protein tyrosine phosphatase (PTP) 1C to the particulate fraction, where it became associated with a 140-150-kD tyrosyl-phosphorylated protein. Western blotting analysis identified this 140-150-kD protein to be CD22. The association of PTP-1C with CD22 was mediated by the NH2-terminal Src homology 2 (SH2) domain of PTP-1C. Complexes of either CD22/PTP-1C/Syk/PLC-gamma(1) could be isolated from B cells stimulated by BCR engagement or a mixture of hydrogen peroxidase and sodium orthovanadate, respectively. The binding of PLC- gamma(1) and Syk to tyrosyl-phosphorylated CD22 was mediated by the NH2- terminal SH2 domain of PLC-gamma(1) and the COOH-terminal SH2 domain of Syk, respectively. These observations suggest that tyrosyl- phosphorylated CD22 may downmodulate the activity of this complex by dephosphorylation of CD22, Syk, and/or PLC-gamma(1). Transient expression of CD22 and a null mutant of PTP-1C (PTP-1CM) in COS cells resulted in an increase in tyrosyl phosphorylation of CD22 and its interaction with PTP-1CM. By contrast, CD22 was not tyrosyl phosphorylated or associated with PTP-1CM in the presence of wild-type PTP-1C. These results suggest that tyrosyl-phosphorylated CD22 may be a substrate for PTP-1C regulates tyrosyl phosphorylation of CD22.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cambier JC, Pleiman CM, Clark MR. Signal transduction by the B cell antigen receptor and its coreceptors. Annu Rev Immunol. 1994;12:457–486. [PubMed]
  • Pleiman CM, D'Ambrosio D, Cambier JC. The B-cell antigen receptor complex: structure and signal transduction. Immunol Today. 1994 Sep;15(9):393–399. [PubMed]
  • Justement LB, Brown VK, Lin J. Regulation of B-cell activation by CD45: a question of mechanism. Immunol Today. 1994 Sep;15(9):399–406. [PubMed]
  • Fearon DT, Carter RH. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu Rev Immunol. 1995;13:127–149. [PubMed]
  • Law CL, Sidorenko SP, Clark EA. Regulation of lymphocyte activation by the cell-surface molecule CD22. Immunol Today. 1994 Sep;15(9):442–449. [PubMed]
  • Kolanus W, Romeo C, Seed B. T cell activation by clustered tyrosine kinases. Cell. 1993 Jul 16;74(1):171–183. [PubMed]
  • Rivera VM, Brugge JS. Clustering of Syk is sufficient to induce tyrosine phosphorylation and release of allergic mediators from rat basophilic leukemia cells. Mol Cell Biol. 1995 Mar;15(3):1582–1590. [PMC free article] [PubMed]
  • Takata M, Sabe H, Hata A, Inazu T, Homma Y, Nukada T, Yamamura H, Kurosaki T. Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways. EMBO J. 1994 Mar 15;13(6):1341–1349. [PubMed]
  • Sidorenko SP, Law CL, Chandran KA, Clark EA. Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):359–363. [PubMed]
  • Sillman AL, Monroe JG. Association of p72syk with the src homology-2 (SH2) domains of PLC gamma 1 in B lymphocytes. J Biol Chem. 1995 May 19;270(20):11806–11811. [PubMed]
  • Powell LD, Varki A. I-type lectins. J Biol Chem. 1995 Jun 16;270(24):14243–14246. [PubMed]
  • Schulte RJ, Campbell MA, Fischer WH, Sefton BM. Tyrosine phosphorylation of CD22 during B cell activation. Science. 1992 Nov 6;258(5084):1001–1004. [PubMed]
  • Leprince C, Draves KE, Geahlen RL, Ledbetter JA, Clark EA. CD22 associates with the human surface IgM-B-cell antigen receptor complex. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3236–3240. [PubMed]
  • Peaker CJ, Neuberger MS. Association of CD22 with the B cell antigen receptor. Eur J Immunol. 1993 Jun;23(6):1358–1363. [PubMed]
  • Pezzutto A, Dörken B, Moldenhauer G, Clark EA. Amplification of human B cell activation by a monoclonal antibody to the B cell-specific antigen CD22, Bp 130/140. J Immunol. 1987 Jan 1;138(1):98–103. [PubMed]
  • Pezzutto A, Rabinovitch PS, Dörken B, Moldenhauer G, Clark EA. Role of the CD22 human B cell antigen in B cell triggering by anti-immunoglobulin. J Immunol. 1988 Mar 15;140(6):1791–1795. [PubMed]
  • Sun H, Tonks NK. The coordinated action of protein tyrosine phosphatases and kinases in cell signaling. Trends Biochem Sci. 1994 Nov;19(11):480–485. [PubMed]
  • Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995 Jan 27;80(2):225–236. [PubMed]
  • Shen SH, Bastien L, Posner BI, Chrétien P. A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature. 1991 Aug 22;352(6337):736–739. [PubMed]
  • Matthews RJ, Bowne DB, Flores E, Thomas ML. Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Biol. 1992 May;12(5):2396–2405. [PMC free article] [PubMed]
  • Plutzky J, Neel BG, Rosenberg RD. Isolation of a src homology 2-containing tyrosine phosphatase. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1123–1127. [PubMed]
  • Yi TL, Cleveland JL, Ihle JN. Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. Mol Cell Biol. 1992 Feb;12(2):836–846. [PMC free article] [PubMed]
  • Shultz LD, Schweitzer PA, Rajan TV, Yi T, Ihle JN, Matthews RJ, Thomas ML, Beier DR. Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell. 1993 Jul 2;73(7):1445–1454. [PubMed]
  • Tsui HW, Siminovitch KA, de Souza L, Tsui FW. Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat Genet. 1993 Jun;4(2):124–129. [PubMed]
  • Shultz LD, Sidman CL. Genetically determined murine models of immunodeficiency. Annu Rev Immunol. 1987;5:367–403. [PubMed]
  • Klingmüller U, Lorenz U, Cantley LC, Neel BG, Lodish HF. Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell. 1995 Mar 10;80(5):729–738. [PubMed]
  • Yi T, Zhang J, Miura O, Ihle JN. Hematopoietic cell phosphatase associates with erythropoietin (Epo) receptor after Epo-induced receptor tyrosine phosphorylation: identification of potential binding sites. Blood. 1995 Jan 1;85(1):87–95. [PubMed]
  • Yi T, Mui AL, Krystal G, Ihle JN. Hematopoietic cell phosphatase associates with the interleukin-3 (IL-3) receptor beta chain and down-regulates IL-3-induced tyrosine phosphorylation and mitogenesis. Mol Cell Biol. 1993 Dec;13(12):7577–7586. [PMC free article] [PubMed]
  • Yi T, Ihle JN. Association of hematopoietic cell phosphatase with c-Kit after stimulation with c-Kit ligand. Mol Cell Biol. 1993 Jun;13(6):3350–3358. [PMC free article] [PubMed]
  • Yeung YG, Berg KL, Pixley FJ, Angeletti RH, Stanley ER. Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in macrophages in response to colony stimulating factor-1. J Biol Chem. 1992 Nov 25;267(33):23447–23450. [PubMed]
  • Tsui FW, Tsui HW. Molecular basis of the motheaten phenotype. Immunol Rev. 1994 Apr;138:185–206. [PubMed]
  • D'Ambrosio D, Hippen KL, Minskoff SA, Mellman I, Pani G, Siminovitch KA, Cambier JC. Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1. Science. 1995 Apr 14;268(5208):293–297. [PubMed]
  • Campbell MA, Klinman NR. Phosphotyrosine-dependent association between CD22 and protein tyrosine phosphatase 1C. Eur J Immunol. 1995 Jun;25(6):1573–1579. [PubMed]
  • Doody GM, Justement LB, Delibrias CC, Matthews RJ, Lin J, Thomas ML, Fearon DT. A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science. 1995 Jul 14;269(5221):242–244. [PubMed]
  • Cyster JG, Goodnow CC. Protein tyrosine phosphatase 1C negatively regulates antigen receptor signaling in B lymphocytes and determines thresholds for negative selection. Immunity. 1995 Jan;2(1):13–24. [PubMed]
  • Torres RM, Law CL, Santos-Argumedo L, Kirkham PA, Grabstein K, Parkhouse RM, Clark EA. Identification and characterization of the murine homologue of CD22, a B lymphocyte-restricted adhesion molecule. J Immunol. 1992 Oct 15;149(8):2641–2649. [PubMed]
  • Zhao Z, Bouchard P, Diltz CD, Shen SH, Fischer EH. Purification and characterization of a protein tyrosine phosphatase containing SH2 domains. J Biol Chem. 1993 Feb 5;268(4):2816–2820. [PubMed]
  • Law CL, Sidorenko SP, Chandran KA, Draves KE, Chan AC, Weiss A, Edelhoff S, Disteche CM, Clark EA. Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex. J Biol Chem. 1994 Apr 22;269(16):12310–12319. [PubMed]
  • Field J, Nikawa J, Broek D, MacDonald B, Rodgers L, Wilson IA, Lerner RA, Wigler M. Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol Cell Biol. 1988 May;8(5):2159–2165. [PMC free article] [PubMed]
  • Leprince C, Draves KE, Ledbetter JA, Torres RM, Clark EA. Characterization of molecular components associated with surface immunoglobulin M in human B lymphocytes: presence of tyrosine and serine/threonine protein kinases. Eur J Immunol. 1992 Aug;22(8):2093–2099. [PubMed]
  • Chalupny NJ, Kanner SB, Schieven GL, Wee SF, Gilliland LK, Aruffo A, Ledbetter JA. Tyrosine phosphorylation of CD19 in pre-B and mature B cells. EMBO J. 1993 Jul;12(7):2691–2696. [PubMed]
  • Tuveson DA, Carter RH, Soltoff SP, Fearon DT. CD19 of B cells as a surrogate kinase insert region to bind phosphatidylinositol 3-kinase. Science. 1993 May 14;260(5110):986–989. [PubMed]
  • Schieven GL, Kirihara JM, Burg DL, Geahlen RL, Ledbetter JA. p72syk tyrosine kinase is activated by oxidizing conditions that induce lymphocyte tyrosine phosphorylation and Ca2+ signals. J Biol Chem. 1993 Aug 5;268(22):16688–16692. [PubMed]
  • Schieven GL, Mittler RS, Nadler SG, Kirihara JM, Bolen JB, Kanner SB, Ledbetter JA. ZAP-70 tyrosine kinase, CD45, and T cell receptor involvement in UV- and H2O2-induced T cell signal transduction. J Biol Chem. 1994 Aug 12;269(32):20718–20726. [PubMed]
  • Townley R, Shen SH, Banville D, Ramachandran C. Inhibition of the activity of protein tyrosine phosphate 1C by its SH2 domains. Biochemistry. 1993 Dec 14;32(49):13414–13418. [PubMed]
  • Pei D, Lorenz U, Klingmüller U, Neel BG, Walsh CT. Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains. Biochemistry. 1994 Dec 27;33(51):15483–15493. [PubMed]
  • Zhao Z, Shen SH, Fischer EH. Stimulation by phospholipids of a protein-tyrosine-phosphatase containing two src homology 2 domains. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4251–4255. [PubMed]
  • Law CL, Torres RM, Sundberg HA, Parkhouse RM, Brannan CI, Copeland NG, Jenkins NA, Clark EA. Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles. J Immunol. 1993 Jul 1;151(1):175–187. [PubMed]
  • Burg DL, Furlong MT, Harrison ML, Geahlen RL. Interactions of Lyn with the antigen receptor during B cell activation. J Biol Chem. 1994 Nov 11;269(45):28136–28142. [PubMed]
  • Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, et al. SH2 domains recognize specific phosphopeptide sequences. Cell. 1993 Mar 12;72(5):767–778. [PubMed]
  • Songyang Z, Shoelson SE, McGlade J, Olivier P, Pawson T, Bustelo XR, Barbacid M, Sabe H, Hanafusa H, Yi T, et al. Specific motifs recognized by the SH2 domains of Csk, 3BP2, fps/fes, GRB-2, HCP, SHC, Syk, and Vav. Mol Cell Biol. 1994 Apr;14(4):2777–2785. [PMC free article] [PubMed]
  • Saouaf SJ, Mahajan S, Rowley RB, Kut SA, Fargnoli J, Burkhardt AL, Tsukada S, Witte ON, Bolen JB. Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9524–9528. [PubMed]
  • Maegawa H, Ugi S, Ishibashi O, Tachikawa-Ide R, Takahara N, Tanaka Y, Takagi Y, Kikkawa R, Shigeta Y, Kashiwagi A. Src homology 2 domains of protein tyrosine phosphatase are phosphorylated by insulin receptor kinase and bind to the COOH-terminus of insulin receptors in vitro. Biochem Biophys Res Commun. 1993 Jul 15;194(1):208–214. [PubMed]
  • Lorenz U, Ravichandran KS, Pei D, Walsh CT, Burakoff SJ, Neel BG. Lck-dependent tyrosyl phosphorylation of the phosphotyrosine phosphatase SH-PTP1 in murine T cells. Mol Cell Biol. 1994 Mar;14(3):1824–1834. [PMC free article] [PubMed]
  • Uchida T, Matozaki T, Noguchi T, Yamao T, Horita K, Suzuki T, Fujioka Y, Sakamoto C, Kasuga M. Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains. J Biol Chem. 1994 Apr 22;269(16):12220–12228. [PubMed]
  • Vogel W, Lammers R, Huang J, Ullrich A. Activation of a phosphotyrosine phosphatase by tyrosine phosphorylation. Science. 1993 Mar 12;259(5101):1611–1614. [PubMed]

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