SH2域
磷酸化
适配器分子crk
酪氨酸磷酸化
信号转导衔接蛋白
癌症研究
酪氨酸
生物
SH3域
阿布勒
断点群集区域
酪氨酸激酶
化学
细胞生物学
原癌基因酪氨酸蛋白激酶Src
信号转导
生物化学
受体
作者
Ron de Jong,Johanna ten Hoeve,Nora Heisterkamp,John Groffen
出处
期刊:Oncogene
[Springer Nature]
日期:1997-02-06
卷期号:14 (5): 507-513
被引量:82
标识
DOI:10.1038/sj.onc.1200885
摘要
BCR/ABL has a causal role in Philadelphia (Ph)-chromosome positive leukemia. The SH2/SH3 adapter protein CRKL is a major substrate of the deregulated BCR/ABL tyrosine kinase and is aberrantly tyrosine-phosphorylated in Ph-positive leukemia cells. In this study, experiments were pursued to identify and analyse the CRKL phosphorylation site(s). In an in vitro kinase assay, CRKL phosphorylation by the abl kinase was limited to a small region between the two CRKL SH3 domains. Within this region, mutation of tyrosine residue 207 yielded a mutant CRKL which could not be phosphorylated by BCR/ABL. Stable overexpression of CRKL or CRKL-Y207F did not transform NIH3T3 cells, while the Y207F mutation eliminated tyrosine-phosphorylation of CRKL. These studies indicate that Y207 in CRKL represents the major in vivo phosphorylation site. Phosphorylation of Y207 provides a binding site for the CRKL SH2 domain and potentially for other SH2-containing proteins. The Y207F mutation in CRKL did not enhance or decrease association with various target signalling proteins, including SOS or C3G, which interact specifically with the CRKL N-SH3 domain. These findings suggest that complex formation with cellular targets is not modulated by CRKL tyrosine-phosphorylation.
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