Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways.
Cellular proteins binding to the first Src homology 3 (SH3) domain of the proto-oncogene product c-Crk indicate Crk-specific signaling pathways.
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发表时间：
1995-04
期刊：
影响因子：
8
通讯作者：
Stephan M. Feller;B. Knudsen;Hidesaburo Hanafusa
中科院分区：
文献类型：
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作者：
Stephan M. Feller;B. Knudsen;Hidesaburo Hanafusa
广泛表达的c-Crk蛋白由一个SH 2和两个SH 3结构域组成，缺乏明显的催化结构域，表明它通过与其他蛋白形成特异性复合物发挥作用。细菌表达的c-Crk通过第一个SH 3结构域[SH 3（N）]在体外形成高度稳定的复合物。最突出的是未知身份的185 kDa蛋白（p185），170 kDa（p170）和145至155 kDa条带的Sos-免疫反应带，对应于最近克隆的C3 G蛋白。p170也与Ash/Grb 2和Nck结合，而p185和C3 G仅与Crk结合。在造血细胞，特别是骨髓单核细胞系中发现了额外的Crk结合蛋白。随后将Crk的蛋白结合特性与CRKL（同源但不同基因的产物）进行比较，发现非常相似。两种鸟嘌呤核苷酸交换因子Sos和C3 G与Crk和CRKL的结合表明Ras或相关蛋白可能通过Crk家族蛋白在信号传导中起作用。
The widely expressed c-Crk protein, composed of one SH2 and two SH3 domains, lacks an apparent catalytic domain, suggesting that it functions through the formation of specific complexes with other proteins. Bacterially expressed c-Crk formed in vitro highly stable complexes via the first SH3 domain [SH3(N)]. Most prominent were a 185 kDa protein of unknown identity (p185), Sos- immunoreactive bands of 170 kDa (p170) and 145 to 155 kDa bands, corresponding to the recently cloned C3G protein. p170 also bound to Ash/Grb2 and Nck while p185 and C3G bound only to Crk. Additional Crk binding proteins were found in hematopoietic cells, particularly the myeloid-monocytic lineage. The protein binding properties of Crk were subsequently compared to CRKL, the product of a homologous but distinct gene, and found to be very similar. The binding of two guanine nucleotide exchange factors, Sos and C3G, to Crk and CRKL indicates that Ras or related proteins likely play a role in signaling through Crk family proteins.