PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Exp Med. 1994 June 1; 179(6): 1747–1756.
PMCID: PMC2191533

CD50 (intercellular adhesion molecule 3) stimulation induces calcium mobilization and tyrosine phosphorylation through p59fyn and p56lck in Jurkat T cell line

Abstract

The leukocyte differentiation antigen, CD50, has been recently identified as the intercellular adhesion molecule 3 (ICAM-3), the third counter-receptor of leukocyte function-associated antigen 1 (LFA-1). This molecule seems to be specially involved in the adhesion events of the initial phases of the immune response. To characterize the role of CD50 in leukocyte interactions, the different molecular events induced after cross-linking of CD50 on T cell-derived Jurkat cell line have been analyzed. When cells were incubated with anti-CD50 mAbs and cross- linked with polyclonal goat anti-mouse immunoglobulins, a rise in intracellular calcium concentration ([Ca2+]i) was observed. This increase in [Ca2+]i was mainly due to the uptake of extracellular Ca2+. This Ca2+ flux involved tyrosine phosphorylations and was further increased by CD3 costimulation. These data, together with those obtained by phosphotyrosine (P-Tyr) immunoprecipitation and in vitro kinase assays, suggested the involvement of protein-tyrosine kinases (PTK) in CD50 transduction pathways. By using specific antisera, the presence of p56lck and p59fyn protein tyrosine kinases (PTK) was clearly demonstrated in the CD50 immunoprecipitates. These findings suggest that the interaction of CD50 with its natural ligand (LFA-1) may result in T lymphocyte activation events, in which CD50 could play a very active role after antigen triggering.

Full Text

The Full Text of this article is available as a PDF (1.3M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Springer TA. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. [PubMed]
  • Kishimoto TK, Larson RS, Corbi AL, Dustin ML, Staunton DE, Springer TA. The leukocyte integrins. Adv Immunol. 1989;46:149–182. [PubMed]
  • Juan M, Vilella R, Mila J, Yagüe J, Miralles A, Campbell KS, Friedrich RJ, Cambier J, Vives J, De Fougerolles AR, et al. CDw50 and ICAM-3: two names for the same molecule. Eur J Immunol. 1993 Jul;23(7):1508–1512. [PubMed]
  • de Fougerolles AR, Stacker SA, Schwarting R, Springer TA. Characterization of ICAM-2 and evidence for a third counter-receptor for LFA-1. J Exp Med. 1991 Jul 1;174(1):253–267. [PMC free article] [PubMed]
  • de Fougerolles AR, Springer TA. Intercellular adhesion molecule 3, a third adhesion counter-receptor for lymphocyte function-associated molecule 1 on resting lymphocytes. J Exp Med. 1992 Jan 1;175(1):185–190. [PMC free article] [PubMed]
  • Vilella R, Mila J, Lozano F, Alberola-Ila J, Places L, Vives J. Involvement of the CDw50 molecule in allorecognition. Tissue Antigens. 1990 Nov;36(5):203–210. [PubMed]
  • Lozano F, Alberola-Ila J, Places L, Vives J. Effect of protein kinase C activators on the phosphorylation and the surface expression of the CDw50 leukocyte antigen. Eur J Biochem. 1992 Jan 15;203(1-2):321–326. [PubMed]
  • Fawcett J, Holness CL, Needham LA, Turley H, Gatter KC, Mason DY, Simmons DL. Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. Nature. 1992 Dec 3;360(6403):481–484. [PubMed]
  • Vazeux R, Hoffman PA, Tomita JK, Dickinson ES, Jasman RL, St John T, Gallatin WM. Cloning and characterization of a new intercellular adhesion molecule ICAM-R. Nature. 1992 Dec 3;360(6403):485–488. [PubMed]
  • de Fougerolles AR, Klickstein LB, Springer TA. Cloning and expression of intercellular adhesion molecule 3 reveals strong homology to other immunoglobulin family counter-receptors for lymphocyte function-associated antigen 1. J Exp Med. 1993 Apr 1;177(4):1187–1192. [PMC free article] [PubMed]
  • Hibbs ML, Jakes S, Stacker SA, Wallace RW, Springer TA. The cytoplasmic domain of the integrin lymphocyte function-associated antigen 1 beta subunit: sites required for binding to intercellular adhesion molecule 1 and the phorbol ester-stimulated phosphorylation site. J Exp Med. 1991 Nov 1;174(5):1227–1238. [PMC free article] [PubMed]
  • Pardi R, Bender JR, Dettori C, Giannazza E, Engleman EG. Heterogeneous distribution and transmembrane signaling properties of lymphocyte function-associated antigen (LFA-1) in human lymphocyte subsets. J Immunol. 1989 Nov 15;143(10):3157–3166. [PubMed]
  • Wacholtz MC, Patel SS, Lipsky PE. Leukocyte function-associated antigen 1 is an activation molecule for human T cells. J Exp Med. 1989 Aug 1;170(2):431–448. [PMC free article] [PubMed]
  • Van Seventer GA, Bonvini E, Yamada H, Conti A, Stringfellow S, June CH, Shaw S. Costimulation of T cell receptor/CD3-mediated activation of resting human CD4+ T cells by leukocyte function-associated antigen-1 ligand intercellular cell adhesion molecule-1 involves prolonged inositol phospholipid hydrolysis and sustained increase of intracellular Ca2+ levels. J Immunol. 1992 Dec 15;149(12):3872–3880. [PubMed]
  • Moy VT, Brian AA. Signaling by lymphocyte function-associated antigen 1 (LFA-1) in B cells: enhanced antigen presentation after stimulation through LFA-1. J Exp Med. 1992 Jan 1;175(1):1–7. [PMC free article] [PubMed]
  • Kuhlman P, Moy VT, Lollo BA, Brian AA. The accessory function of murine intercellular adhesion molecule-1 in T lymphocyte activation. Contributions of adhesion and co-activation. J Immunol. 1991 Mar 15;146(6):1773–1782. [PubMed]
  • Fischer H, Gjörloff A, Hedlund G, Hedman H, Lundgren E, Kalland T, Sjögren HO, Dohlsten M. Stimulation of human naive and memory T helper cells with bacterial superantigen. Naive CD4+45RA+ T cells require a costimulatory signal mediated through the LFA-1/ICAM-1 pathway. J Immunol. 1992 Apr 1;148(7):1993–1998. [PubMed]
  • Damle NK, Klussman K, Linsley PS, Aruffo A, Ledbetter JA. Differential regulatory effects of intercellular adhesion molecule-1 on costimulation by the CD28 counter-receptor B7. J Immunol. 1992 Oct 15;149(8):2541–2548. [PubMed]
  • Damle NK, Klussman K, Aruffo A. Intercellular adhesion molecule-2, a second counter-receptor for CD11a/CD18 (leukocyte function-associated antigen-1), provides a costimulatory signal for T-cell receptor-initiated activation of human T cells. J Immunol. 1992 Feb 1;148(3):665–671. [PubMed]
  • Martorell J, Rojo I, Vilella R, Martinez-Caceres E, Vives J. CD27 induction on thymocytes. J Immunol. 1990 Sep 1;145(5):1356–1363. [PubMed]
  • Martorell J, Vilella R, Borche L, Rojo I, Vives J. A second signal for T cell mitogenesis provided by monoclonal antibodies CD45 (T200). Eur J Immunol. 1987 Oct;17(10):1447–1451. [PubMed]
  • Marth JD, Lewis DB, Wilson CB, Gearn ME, Krebs EG, Perlmutter RM. Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases. EMBO J. 1987 Sep;6(9):2727–2734. [PubMed]
  • Justement LB, Wienands J, Hombach J, Reth M, Cambier JC. Membrane IgM and IgD molecules fail to transduce Ca2+ mobilizing signals when expressed on differentiated B lineage cells. J Immunol. 1990 May 1;144(9):3272–3280. [PubMed]
  • Alberola-Ila J, Places L, Lozano F, Vives J. Association of an activation inducible serine kinase activity with CD5. J Immunol. 1993 Nov 1;151(9):4423–4430. [PubMed]
  • Lozano F, Alberola-Ila J, Places L, Gallart T, Vives J. Phosphorylation-mediated changes in the electrophoretic mobility of CD5 molecules. Eur J Biochem. 1990 Oct 24;193(2):469–477. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Samelson LE, Phillips AF, Luong ET, Klausner RD. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358–4362. [PubMed]
  • Oettgen HC, Pettey CL, Maloy WL, Terhorst C. A T3-like protein complex associated with the antigen receptor on murine T cells. Nature. 1986 Mar 20;320(6059):272–275. [PubMed]
  • Markwell MA, Fox CF. Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril. Biochemistry. 1978 Oct 31;17(22):4807–4817. [PubMed]
  • Trevillyan JM, Lu YL, Atluru D, Phillips CA, Bjorndahl JM. Differential inhibition of T cell receptor signal transduction and early activation events by a selective inhibitor of protein-tyrosine kinase. J Immunol. 1990 Nov 15;145(10):3223–3230. [PubMed]
  • June CH, Fletcher MC, Ledbetter JA, Schieven GL, Siegel JN, Phillips AF, Samelson LE. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722–7726. [PubMed]
  • Tonks NK, Charbonneau H, Diltz CD, Fischer EH, Walsh KA. Demonstration that the leukocyte common antigen CD45 is a protein tyrosine phosphatase. Biochemistry. 1988 Nov 29;27(24):8695–8701. [PubMed]
  • Samelson LE, Fletcher MC, Ledbetter JA, June CH. Activation of tyrosine phosphorylation in human T cells via the CD2 pathway. Regulation by the CD45 tyrosine phosphatase. J Immunol. 1990 Oct 15;145(8):2448–2454. [PubMed]
  • Veillette A, Bookman MA, Horak EM, Bolen JB. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. [PubMed]
  • Ley SC, Davies AA, Druker B, Crumpton MJ. The T cell receptor/CD3 complex and CD2 stimulate the tyrosine phosphorylation of indistinguishable patterns of polypeptides in the human T leukemic cell line Jurkat. Eur J Immunol. 1991 Sep;21(9):2203–2209. [PubMed]
  • Malissen B, Schmitt-Verhulst AM. Transmembrane signalling through the T-cell-receptor-CD3 complex. Curr Opin Immunol. 1993 Jun;5(3):324–333. [PubMed]
  • Shenoy-Scaria AM, Kwong J, Fujita T, Olszowy MW, Shaw AS, Lublin DM. Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1. J Immunol. 1992 Dec 1;149(11):3535–3541. [PubMed]
  • Carmo AM, Mason DW, Beyers AD. Physical association of the cytoplasmic domain of CD2 with the tyrosine kinases p56lck and p59fyn. Eur J Immunol. 1993 Sep;23(9):2196–2201. [PubMed]
  • Shin J, Doyle C, Yang Z, Kappes D, Strominger JL. Structural features of the cytoplasmic region of CD4 required for internalization. EMBO J. 1990 Feb;9(2):425–434. [PubMed]
  • Turner JM, Brodsky MH, Irving BA, Levin SD, Perlmutter RM, Littman DR. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 1990 Mar 9;60(5):755–765. [PubMed]
  • Beyers AD, Spruyt LL, Williams AF. Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2945–2949. [PubMed]
  • Friedrich B, Cantrell DA, Gullberg M. Evidences for protein kinase C. Activation in T lymphocytes by stimulation of either the CD2 or CD3 antigens. Eur J Immunol. 1989 Jan;19(1):17–23. [PubMed]
  • Alsinet E, Inglés-Esteve J, Vilella R, Lozano F, Milá J, Rojo I, Martorell J, Vives J, Gayá A. Differential effects of anti-CD45 monoclonal antibody on human B cell proliferation: a monoclonal antibody recognizing a neuraminidase-sensitive epitope of the T200 molecule enhances anti-immunoglobulin-induced proliferation. Eur J Immunol. 1990 Dec;20(12):2801–2804. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press