The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin αIIbβ3-mediated adhesion and spreading
The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin αIIbβ3-mediated adhesion and spreading
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DOI：
10.1074/jbc.m105363200
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发表时间：
2002-03-08
影响因子：
4.8
通讯作者：
Heisterkamp, N
中科院分区：
文献类型：
--
作者：
Haataja, L;Kaartinen, V;Heisterkamp, N
人类只有三种小GTdR ae亚型，它们共同调节各种细胞过程，包括与肌动蛋白细胞骨架重组相关的过程。Rac3在整合素介导的粘附和扩散中的作用尚未确定。我们在这里报告，CIB，一种与α（IIb）β（3）纤维蛋白原受体结合的蛋白质，只与活化的（V12）Rac 3相互作用，而不与Rac 1或Rac 2相互作用。V12Rac 3与CIB的结合由Rac 3的C末端和Rac 3膜定位介导。纤维蛋白原上的细胞粘附伴随着特定的Rac 3的水平增加，但不是Rac 1或Rac 2的Triton不溶性部分的细胞。此外，CIB与活性Rac 3共定位于粘附纤维蛋白原的细胞的外周。V12Rac 3和CIB的表达刺激α（IIb）β（3）介导的粘附和在纤维蛋白原上的铺展。此外，通过α（IIb）β（3）的粘附引起内源性GTP结合Rac 3水平的显著增加，但Rac 1没有。这些综合结果强烈暗示Rac3和CIB在α（IIb）β（3）介导的粘附过程中与整合素相关的细胞骨架重组。
There are only three human isoforms of the small GTPase Rae, which together regulate a variety of cellular processes, including those related to actin cytoskeletal reorganization. A role for Rac3 in integrin-mediated adhesion and spreading has not been defined. We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization. Adhesion of cells on fibrinogen was accompanied by a specific increase in the levels of Rac3 but not Rac1 or Rac2 in the Triton-insoluble fraction of the cell. Also, CIB co-localized with active Rac3 to the periphery of cells adhering to fibrinogen. Expression of V12Rac3 and CIB stimulated alpha(IIb)beta(3)-mediated adhesion and spreading on fibrinogen. Moreover, adhesion through alpha(IIb)beta(3) caused a marked increase in the levels of endogenous GTP-bound Rac3 but not Rac1. These combined results strongly implicate Rac3 and CIB in integrin-associated cytoskeletal reorganization during alpha(IIb)beta(3)-mediated adhesion.