Requirements for localization of p130(cas) to focal adhesions

被引:138
作者
Nakamoto, T
Sakai, R
Honda, H
Ogawa, S
Ueno, H
Suzuki, T
Aizawa, S
Yazaki, Y
Hirai, H
机构
[1] UNIV TOKYO, FAC MED, DEPT INTERNAL MED 3, TOKYO 113, JAPAN
[2] KUMAMOTO UNIV, SCH MED, DEPT MORPHOGENESIS, INST MOL EMBRYOL & GENET, KUMAMOTO 860, JAPAN
关键词
D O I
10.1128/MCB.17.7.3884
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
p130(cas) (Gas) is an adapter protein that has an SH3 domain followed by multiple SH2 binding motifs in the substrate domain. It also contains a tyrosine residue and a proline-rich sequence near the C terminus, which are the binding sites for the SH2 and SH3 domains of Src kinase, respective?v. Cas was originally identified as a major tyrosine-phosphorylated protein in v-Crk- and v-Src-transformed cells. Subsequently, Cas was shown to be inducibly tyrosine phosphorylated upon integrin stimulation; it is therefore regarded as one of the focal adhesion proteins, Using an immunofluorescence study, rye examined the subcellular localization of Cas and determined the regions required for its localization to focal adhesions, In nontransformed cells, Cas was localized predominantly to the cytoplasm and partially to focal adhesions, However, in 527F-c-Src-transformed cells, Cas was localized mainly to podosomes, where the focal adhesion proteins are assembled, The localization of Cas to focal adhesions was also observed in cells expressing the kinase-negative 527F/295M-c-Src. A series of analyses with deletion mutants expressed in various cells revealed that the SH3 domain of Cas is necessary for its localization to focal adhesions in nontransformed cells while both the SH3 domain and the C-terminal Src binding domain of Cas are required in 527F-c-Src-transformed cells and fibronectin-stimulated cells. In addition, the localization of Cas to focal adhesions was abolished in Src-negative cells, These results demonstrate that the SH3 domain of Cas and the association of Cas with Src kinase play a pivotal role in the localization of Cas to focal adhesions.
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页码:3884 / 3897
页数:14
相关论文
共 44 条
  • [1] Coordinate activation of c-Src by SH3- and SH2-binding sites on a novel, p130(Cas)-related protein, Sin
    Alexandropoulos, K
    Baltimore, D
    [J]. GENES & DEVELOPMENT, 1996, 10 (11) : 1341 - 1355
  • [2] IDENTIFICATION AND CHARACTERIZATION OF A NOVEL RELATED ADHESION FOCAL TYROSINE KINASE (RAFTK) FROM MEGAKARYOCYTES AND BRAIN
    AVRAHAM, S
    LONDON, R
    FU, YG
    OTA, S
    HIREGOWDARA, D
    LI, JZ
    JIANG, SX
    PASZTOR, LN
    WHITE, RA
    GROOPMAN, JE
    AVRAHAM, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (46) : 27742 - 27751
  • [3] BERGMAN M, 1995, MOL CELL BIOL, V15, P711
  • [4] BOCKHOLT SM, 1993, J BIOL CHEM, V268, P14565
  • [5] AN EXAMINATION OF FOCAL ADHESION FORMATION AND TYROSINE PHOSPHORYLATION IN FIBROBLASTS ISOLATED FROM SRC(-), FYN(-), AND YES(-) MICE
    BOCKHOLT, SM
    BURRIDGE, K
    [J]. CELL ADHESION AND COMMUNICATION, 1995, 3 (02) : 91 - 100
  • [6] Burnham MR, 1996, ONCOGENE, V12, P2467
  • [7] TYROSINE PHOSPHORYLATION OF PAXILLIN AND PP125(FAK) ACCOMPANIES CELL-ADHESION TO EXTRACELLULAR-MATRIX - A ROLE IN CYTOSKELETAL ASSEMBLY
    BURRIDGE, K
    TURNER, CE
    ROMER, LH
    [J]. JOURNAL OF CELL BIOLOGY, 1992, 119 (04) : 893 - 903
  • [8] FOCAL ADHESIONS - TRANSMEMBRANE JUNCTIONS BETWEEN THE EXTRACELLULAR-MATRIX AND THE CYTOSKELETON
    BURRIDGE, K
    FATH, K
    KELLY, T
    NUCKOLLS, G
    TURNER, C
    [J]. ANNUAL REVIEW OF CELL BIOLOGY, 1988, 4 : 487 - 525
  • [9] INTEGRINS AND SIGNAL-TRANSDUCTION PATHWAYS - THE ROAD TAKEN
    CLARK, EA
    BRUGGE, JS
    [J]. SCIENCE, 1995, 268 (5208) : 233 - 239
  • [10] REGULATION OF FOCAL ADHESION-ASSOCIATED PROTEIN TYROSINE KINASE BY BOTH CELLULAR ADHESION AND ONCOGENIC TRANSFORMATION
    GUAN, JL
    SHALLOWAY, D
    [J]. NATURE, 1992, 358 (6388) : 690 - 692