SUPPRESSION OF C-SRC ACTIVITY BY C-TERMINAL SRC KINASE INVOLVES THE C-SRC SH2-DOMAIN AND SH3-DOMAIN - ANALYSIS WITH SACCHAROMYCES-CEREVISIAE

被引:137
作者
MURPHY, SM
BERGMAN, M
MORGAN, DO
机构
[1] UNIV CALIF SAN FRANCISCO, DEPT PHYSIOL, SAN FRANCISCO, CA 94143 USA
[2] UNIV HELSINKI, DEPT PATHOL, SF-00014 HELSINKI, FINLAND
关键词
D O I
10.1128/MCB.13.9.5290
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The kinase activity of c-Src is normally repressed in vertebrate cells by extensive phosphorylation of Y-527. C-terminal Src kinase (CSK) is a candidate for the enzyme that catalyzes this phosphorylation. We have used budding yeast to study the regulation of c-Src activity by CSK in intact cells. Expression of c-Src in Saccharomyces cerevisiae, which lacks endogenous c-Src and Y-527 kinases, induces a kinase-dependent growth inhibition. Coexpression of CSK in these cells results in phosphorylation of c-Src on Y-527 and suppression of the c-Src phenotype. CSK does not fully suppress the activity of c-Src mutants lacking portions of the SH2 or SH3 domains, even though these mutant proteins are phosphorylated on Y-527 by CSK both in vivo and in vitro. These results suggest that both the SH2 and SH3 domains of c-Src are required for the suppression of c-Src activity by Y-527 phosphorylation.
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收藏
页码:5290 / 5300
页数:11
相关论文
共 53 条
  • [1] THE HUMAN P50(CSK) TYROSINE KINASE PHOSPHORYLATES P56(LCK) AT TYR-505 AND DOWN REGULATES ITS CATALYTIC ACTIVITY
    BERGMAN, M
    MUSTELIN, T
    OETKEN, C
    PARTANEN, J
    FLINT, NA
    AMREIN, KE
    AUTERO, M
    BURN, P
    ALITALO, K
    [J]. EMBO JOURNAL, 1992, 11 (08) : 2919 - 2924
  • [2] CELL-TRANSFORMATION BY PP60C-SRC MUTATED IN THE CARBOXY-TERMINAL REGULATORY DOMAIN
    CARTWRIGHT, CA
    ECKHART, W
    SIMON, S
    KAPLAN, PL
    [J]. CELL, 1987, 49 (01) : 83 - 91
  • [3] IDENTIFICATION OF A PROTEIN THAT BINDS TO THE SH3 REGION OF ABI AND IS SIMILAR TO BCR AND GAP-RHO
    CICCHETTI, P
    MAYER, BJ
    THIEL, G
    BALTIMORE, D
    [J]. SCIENCE, 1992, 257 (5071) : 803 - 806
  • [4] REDISTRIBUTION OF ACTIVATED PP60C-SRC TO INTEGRIN-DEPENDENT CYTOSKELETAL COMPLEXES IN THROMBIN-STIMULATED PLATELETS
    CLARK, EA
    BRUGGE, JS
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (03) : 1863 - 1871
  • [5] Cooper J.A, 1990, PEPT PROT PHOSPH, P85
  • [6] TYR527 IS PHOSPHORYLATED IN PP60C-SRC - IMPLICATIONS FOR REGULATION
    COOPER, JA
    GOULD, KL
    CARTWRIGHT, CA
    HUNTER, T
    [J]. SCIENCE, 1986, 231 (4744) : 1431 - 1434
  • [7] DEPHOSPHORYLATION OR ANTIBODY-BINDING TO THE CARBOXY TERMINUS STIMULATES PP60C-SRC
    COOPER, JA
    KING, CS
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1986, 6 (12) : 4467 - 4477
  • [8] COOPER JA, 1987, ONCOGENE RES, V1, P297
  • [9] CORRECTIONS
    CZERNILOFSKY, AP
    [J]. NATURE, 1983, 301 (5902) : 736 - 738
  • [10] DELETIONS IN THE SH2 DOMAIN OF P60V-SRC PREVENT ASSOCIATION WITH THE DETERGENT-INSOLUBLE CELLULAR MATRIX
    FUKUI, Y
    OBRIEN, MC
    HANAFUSA, H
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (03) : 1207 - 1213