Functions of the adapter protein Cas: signal convergence and the determination of cellular responses

被引:171
作者
Bouton, AH [1 ]
Riggins, RB [1 ]
Bruce-Staskal, PJ [1 ]
机构
[1] Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Charlottesville, VA 22908 USA
基金
美国国家科学基金会;
关键词
Cas; Src; Crk; Rac1; migration; adapter;
D O I
10.1038/sj.onc.1204785
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
Since Cas was first identified as a highly phosphorylated 130 kilodalton protein that associated with the v-Src and v-Crk-oncoproteins, considerable effort has been made to determine its function. Its predicted role as a scaffolding molecule based on its domain structure has been largely confirmed. Through its ability to undergo rapid changes in phosphorylation, subcellular localization and association with heterologous proteins, Cas may spatially and temporally regulate the function of its binding partners. Numerous proteins have been identified that bind to Cas in vitro and/or in vivo, but in only a few cases is there an understanding of how Cas may function in these protein complexes. To date, Cas-Crk and Cas-Src complexes have been most frequently implicated in Cas function, particularly in regards to processes involving regulation of the actin cytoskeleton and proliferation. These and other Cas protein complexes contribute to the critical role of Cas in cell adhesion, migration, proliferation and survival of normal cycling cells. However, under conditions in which these processes are deregulated, Cas appears to play a role in oncogenic transformation and perhaps metastasis. Therefore, in its capacity as an adapter protein, Cas serves as a point of convergence for many distinct signaling inputs, ultimately contributing to the generation of specific cellular responses.
引用
收藏
页码:6448 / 6458
页数:11
相关论文
共 140 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] Matrix survival signaling:: From fibronectin via focal adhesion kinase to c-Jun NH2-terminal kinase
    Almeida, EAC
    Ilic, D
    Han, Q
    Hauck, CR
    Jin, F
    Kawakatsu, H
    Schlaepfer, DD
    Damsky, CH
    [J]. JOURNAL OF CELL BIOLOGY, 2000, 149 (03) : 741 - 754
  • [3] YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis
    Andersson, K
    Carballeira, N
    Magnusson, KE
    Persson, C
    Stendahl, O
    WolfWatz, H
    Fallman, M
    [J]. MOLECULAR MICROBIOLOGY, 1996, 20 (05) : 1057 - 1069
  • [4] Aplin AE, 1999, J CELL SCI, V112, P695
  • [5] CrkL activates integrin-mediated hematopoietic cell adhesion through the guanine nucleotide exchange factor C3G
    Arai, A
    Nosaka, Y
    Kohsaka, H
    Miyasaka, N
    Miura, O
    [J]. BLOOD, 1999, 93 (11) : 3713 - 3722
  • [6] Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells:: Potential relevance to neoplastic lymphohematopoietic cells
    Astier, A
    Manié, SN
    Law, SF
    Canty, T
    Haghayghi, N
    Druker, BJ
    Salgia, R
    Golemis, EA
    Freedman, AS
    [J]. LEUKEMIA & LYMPHOMA, 1997, 28 (1-2) : 65 - 72
  • [7] The related adhesion focal tyrosine kinase differentially phosphorylates p130(Cas) and the Cas-like protein, p105(HEF1)
    Astier, A
    Manie, SN
    Avraham, H
    Hirai, H
    Law, SF
    Zhang, YH
    Golemis, EA
    Fu, YG
    Druker, BJ
    Haghayeghi, N
    Freedman, AS
    Avraham, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (32) : 19719 - 19724
  • [8] AUVINEN M, 1995, MOL CELL BIOL, V15, P6513
  • [9] Bacterial lipopolysaccharide disrupts endothelial monolayer integrity and survival signaling events through caspase cleavage of adherens junction proteins
    Bannerman, DD
    Sathyamoorthy, M
    Goldblum, SE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (52) : 35371 - 35380
  • [10] Biscardi JS, 1998, MOL CARCINOGEN, V21, P261, DOI 10.1002/(SICI)1098-2744(199804)21:4<261::AID-MC5>3.0.CO