PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
 
Mol Cell Biol. 1996 April; 16(4): 1305–1315.
PMCID: PMC231114

Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk.

Abstract

Antigen receptor ligation on lymphocytes activates protein tyrosine kinases and phospholipase C-gamma (PLC-gamma) isoforms. Glutathione S-transferase fusion proteins containing the C-terminal Src-homology 2 [SH2(C)] domain of PLC-gamma1 bound to tyrosyl phosphorylated Syk. Syk isolated from antigen receptor-activated B cells phosphorylated PLC-gamma1 on Tyr-771 and the key regulatory residue Tyr-783 in vitro, whereas Lyn from the same B cells phosphorylated PLC-gamma1 only on Tyr-771. The ability of Syk to phosphorylate PLC-gamma1 required antigen receptor ligation, while Lyn was constitutively active. An mCD8-Syk cDNA construct could be expressed as a tyrosyl-phosphorylated chimeric protein tyrosine kinase in COS cells, was recognized by PLC-gamma1 SH2(C) in vitro, and induced tyrosyl phosphorylation of endogenous PLC-gamma1 in vivo. Substitution of Tyr-525 and Tyr-526 at the autophosphorylation site of Syk in mCD8-Syk substantially reduced the kinase activity and the binding of this variant chimera to PLC-gamma1 SH2(C) in vitro; it also failed to induce tyrosyl phosphorylation of PLC-gamma1 in vivo. In contrast, substitution of Tyr-348 and Tyr-352 in the linker region of Syk in mCD8-Syk did not affect the kinase activity of this variant chimera but almost completely eliminated its binding to PLC-gamma1 SH(C) and completely eliminated its ability to induce tyrosyl phosphorylation of PLC-gamma1 in vivo. Thus, an optimal kinase activity of Syk and an interaction between the linker region of Syk with PLC-gamma1 are required for the tyrosyl phosphorylation of PLC-gamma1.

Full Text

The Full Text of this article is available as a PDF (859K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Arpaia E, Shahar M, Dadi H, Cohen A, Roifman CM. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell. 1994 Mar 11;76(5):947–958. [PubMed]
  • Berridge MJ. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. [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]
  • 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]
  • Carraway KL, 3rd, Cantley LC. A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling. Cell. 1994 Jul 15;78(1):5–8. [PubMed]
  • Carter RH, Park DJ, Rhee SG, Fearon DT. Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2745–2749. [PubMed]
  • Chan AC, Kadlecek TA, Elder ME, Filipovich AH, Kuo WL, Iwashima M, Parslow TG, Weiss A. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science. 1994 Jun 10;264(5165):1599–1601. [PubMed]
  • Claesson-Welsh L. Platelet-derived growth factor receptor signals. J Biol Chem. 1994 Dec 23;269(51):32023–32026. [PubMed]
  • Elder ME, Lin D, Clever J, Chan AC, Hope TJ, Weiss A, Parslow TG. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science. 1994 Jun 10;264(5165):1596–1599. [PubMed]
  • Hempel WM, Schatzman RC, DeFranco AL. Tyrosine phosphorylation of phospholipase C-gamma 2 upon cross-linking of membrane Ig on murine B lymphocytes. J Immunol. 1992 May 15;148(10):3021–3027. [PubMed]
  • Hutchcroft JE, Harrison ML, Geahlen RL. Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor. J Biol Chem. 1992 Apr 25;267(12):8613–8619. [PubMed]
  • Hutchcroft JE, Harrison ML, Geahlen RL. B lymphocyte activation is accompanied by phosphorylation of a 72-kDa protein-tyrosine kinase. J Biol Chem. 1991 Aug 15;266(23):14846–14849. [PubMed]
  • Kim HK, Kim JW, Zilberstein A, Margolis B, Kim JG, Schlessinger J, Rhee SG. PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254. Cell. 1991 May 3;65(3):435–441. [PubMed]
  • Kim JW, Sim SS, Kim UH, Nishibe S, Wahl MI, Carpenter G, Rhee SG. Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro. J Biol Chem. 1990 Mar 5;265(7):3940–3943. [PubMed]
  • Kolanus W, Romeo C, Seed B. T cell activation by clustered tyrosine kinases. Cell. 1993 Jul 16;74(1):171–183. [PubMed]
  • Kong GH, Bu JY, Kurosaki T, Shaw AS, Chan AC. Reconstitution of Syk function by the ZAP-70 protein tyrosine kinase. Immunity. 1995 May;2(5):485–492. [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]
  • 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]
  • 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]
  • Liao F, Shin HS, Rhee SG. In vitro tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2 by src-family protein tyrosine kinases. Biochem Biophys Res Commun. 1993 Mar 31;191(3):1028–1033. [PubMed]
  • Malek SN, Desiderio S. SH2 domains of the protein-tyrosine kinases Blk, Lyn, and Fyn(T) bind distinct sets of phosphoproteins from B lymphocytes. J Biol Chem. 1993 Oct 25;268(30):22557–22565. [PubMed]
  • Mohammadi M, Dionne CA, Li W, Li N, Spivak T, Honegger AM, Jaye M, Schlessinger J. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature. 1992 Aug 20;358(6388):681–684. [PubMed]
  • Nishibe S, Wahl MI, Hernández-Sotomayor SM, Tonks NK, Rhee SG, Carpenter G. Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation. Science. 1990 Nov 30;250(4985):1253–1256. [PubMed]
  • Park DJ, Rho HW, Rhee SG. CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453–5456. [PubMed]
  • Pascal SM, Singer AU, Gish G, Yamazaki T, Shoelson SE, Pawson T, Kay LE, Forman-Kay JD. Nuclear magnetic resonance structure of an SH2 domain of phospholipase C-gamma 1 complexed with a high affinity binding peptide. Cell. 1994 May 6;77(3):461–472. [PubMed]
  • Pawson T. Protein modules and signalling networks. Nature. 1995 Feb 16;373(6515):573–580. [PubMed]
  • Pleiman CM, Clark MR, Gauen LK, Winitz S, Coggeshall KM, Johnson GL, Shaw AS, Cambier JC. Mapping of sites on the Src family protein tyrosine kinases p55blk, p59fyn, and p56lyn which interact with the effector molecules phospholipase C-gamma 2, microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase. Mol Cell Biol. 1993 Sep;13(9):5877–5887. [PMC free article] [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]
  • 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]
  • Rotin D, Margolis B, Mohammadi M, Daly RJ, Daum G, Li N, Fischer EH, Burgess WH, Ullrich A, Schlessinger J. SH2 domains prevent tyrosine dephosphorylation of the EGF receptor: identification of Tyr992 as the high-affinity binding site for SH2 domains of phospholipase C gamma. EMBO J. 1992 Feb;11(2):559–567. [PubMed]
  • Rowley RB, Bolen JB, Fargnoli J. Molecular cloning of rodent p72Syk. Evidence of alternative mRNA splicing. J Biol Chem. 1995 May 26;270(21):12659–12664. [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, Kirihara JM, Myers DE, Ledbetter JA, Uckun FM. Reactive oxygen intermediates activate NF-kappa B in a tyrosine kinase-dependent mechanism and in combination with vanadate activate the p56lck and p59fyn tyrosine kinases in human lymphocytes. Blood. 1993 Aug 15;82(4):1212–1220. [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]
  • 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]
  • 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]
  • 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]
  • Valius M, Bazenet C, Kazlauskas A. Tyrosines 1021 and 1009 are phosphorylation sites in the carboxy terminus of the platelet-derived growth factor receptor beta subunit and are required for binding of phospholipase C gamma and a 64-kilodalton protein, respectively. Mol Cell Biol. 1993 Jan;13(1):133–143. [PMC free article] [PubMed]
  • Valius M, Kazlauskas A. Phospholipase C-gamma 1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal. Cell. 1993 Apr 23;73(2):321–334. [PubMed]
  • Wahl MI, Nishibe S, Kim JW, Kim H, Rhee SG, Carpenter G. Identification of two epidermal growth factor-sensitive tyrosine phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells. J Biol Chem. 1990 Mar 5;265(7):3944–3948. [PubMed]
  • Zhu G, Decker SJ, Saltiel AR. Direct analysis of the binding of Src-homology 2 domains of phospholipase C to the activated epidermal growth factor receptor. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9559–9563. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)