Focal adhesion kinase-related fakB is regulated by the integrin LFA-1 and interacts with the SH3 domain of phospholipase C gamma 1

被引:17
作者
Kanner, SB
机构
[1] Bristol-Myers Squibb P., Seattle
关键词
D O I
10.1006/cimm.1996.0188
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Signal transduction through integrin molecules expressed on platelets and nonlymphoid cells involves activation of the intracellular focal adhesion kinase pp125(FAK) (FAK) to phosphorylate substrate proteins on tyrosine residues. Similar mechanisms are also functional in T-lymphocytes through the beta(1)-integrin VLA-4. A putative PAR-related phosphoprotein (fakB) was identified that is responsive to intracellular signals induced through ligation of antigen receptors on both T- and B-lymphocytes, and whose induced tyrosine phosphorylation is augmented by TCR costimulation through the adhesion/costimulatory receptors CD2 and CD4. In this report, fakB is shown to respond to extracellular signals through the beta(2)-integrin LFA-1 in the absence of primary signals through the TCR. Protein-protein complex formation was observed involving an association between fakB, phospholipase C gamma 1 (PLC gamma 1), and the tyrosine phosphoprotein pp35-36. Evidence is provided here that fakB interacts with PLC gamma 1 through its SH3 domain. The association between fakB and PLC gamma 1 does not appear to require T-cell activation, whereas the induced tyrosine phosphorylation of the protein complex components occurs following engagement of LFA-1. These data indicate that the beta(2)-integrin LFA-1 expressed on T-lymphocytes stimulates a novel PAR-related molecule that may function in the interplay between adhesion receptors and intracellular signaling enzymes responsible for downstream second messenger generation. (C) 1996 Academic Press, Inc.
引用
收藏
页码:164 / 169
页数:6
相关论文
共 40 条
  • [1] INDUCTION OF TYROSINE PHOSPHORYLATION DURING ICAM-3 AND LFA-1-MEDIATED INTERCELLULAR-ADHESION, AND ITS REGULATION BY THE CD45 TYROSINE PHOSPHATASE
    ARROYO, AG
    CAMPANERO, MR
    SANCHEZMATEOS, P
    ZAPATA, JM
    URSA, MA
    DELPOZO, MA
    SANCHEZMADRID, F
    [J]. JOURNAL OF CELL BIOLOGY, 1994, 126 (05) : 1277 - 1286
  • [2] SH3 DOMAINS DIRECT CELLULAR-LOCALIZATION OF SIGNALING MOLECULES
    BARSAGI, D
    ROTIN, D
    BATZER, A
    MANDIYAN, V
    SCHLESSINGER, J
    [J]. CELL, 1993, 74 (01) : 83 - 91
  • [3] BEATTY PG, 1983, J IMMUNOL, V131, P2913
  • [4] INTEGRINS AND SIGNAL-TRANSDUCTION PATHWAYS - THE ROAD TAKEN
    CLARK, EA
    BRUGGE, JS
    [J]. SCIENCE, 1995, 268 (5208) : 233 - 239
  • [5] MODULAR BINDING DOMAINS IN SIGNAL-TRANSDUCTION PROTEINS
    COHEN, GB
    REN, RB
    BALTIMORE, D
    [J]. CELL, 1995, 80 (02) : 237 - 248
  • [6] DONOVAN JA, 1994, J BIOL CHEM, V269, P22921
  • [7] 2 BINDING ORIENTATIONS FOR PEPTIDES TO THE SRC SH3 DOMAIN - DEVELOPMENT OF A GENERAL-MODEL FOR SH3-LIGAND INTERACTIONS
    FENG, SB
    CHEN, JK
    YU, HT
    SIMON, JA
    SCHREIBER, SL
    [J]. SCIENCE, 1994, 266 (5188) : 1241 - 1247
  • [8] T-CELL ACTIVATION-DEPENDENT ASSOCIATION BETWEEN THE P85 SUBUNIT OF THE PHOSPHATIDYLINOSITOL 3-KINASE AND GRB2/PHOSPHOLIPASE C-GAMMA-1-BINDING PHOSPHOTYROSYL PROTEIN PP36/38
    FUKAZAWA, T
    REEDQUIST, KA
    PANCHAMOORTHY, G
    SOLTOFF, S
    TRUB, T
    DRUKER, B
    CANTLEY, L
    SHOELSON, SE
    BAND, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (34) : 20177 - 20182
  • [9] THE SH3 DOMAIN-BINDING T-CELL TYROSYL PHOSPHOPROTEIN P120 - DEMONSTRATION OF ITS IDENTITY WITH THE C-CBL PROTOONCOGENE PRODUCT AND IN-VIVO COMPLEXES WITH FYN, GRB2, AND PHOSPHATIDYLINOSITOL 3-KINASE
    FUKAZAWA, T
    REEDQUIST, KA
    TRUB, T
    SOLTOFF, S
    PANCHAMOORTHY, G
    DRUKER, B
    CANTLEY, L
    SHOELSON, SE
    BAND, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (32) : 19141 - 19150
  • [10] GILLILAND LK, 1992, J BIOL CHEM, V267, P13610