Sattler M, Salgia R
Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Leukemia. 1998 May;12(5):637-44. doi: 10.1038/sj.leu.2401010.
CRKL is a 39 kDa adapter protein, originally cloned in proximity to the BCR gene on chromosome 22, which has a key regulatory role in hematopoietic cells. CRKL has one SH2 and two SH3 domains, with 60% homology to CRK II. CRKL is a prominent substrate of the BCR/ABL oncoprotein in chronic myelogenous leukemia and binds to both BCR/ABL and c-ABL. CRKL has been shown to be tryosine phosphorylated in response to normal hematopoietic growth factor receptor signaling with ligands such as thrombopoietin, erythropoietin or steel factor. Additionally, CRKL is involved in signaling initiated by crosslinking of beta integrins, and B cell or T cell receptors. Structurally, the amino-terminal SH3 domain of CRKL has been shown to bind proteins such as C3G, SOS, PI3-K, c-ABL or BCR/ABL. The SH2 domain of CRKL can bind to tyrosine phosphorylated proteins such as CBL, HEF1, CAS or paxillin. This review summarizes the current knowledge on the function of this unique adapter protein in normal hematopoietic and leukemic cell signaling.
CRKL是一种39kDa的衔接蛋白，最初是在22号染色体上靠近BCR基因的位置克隆得到的，它在造血细胞中具有关键的调节作用。CRKL有一个SH2结构域和两个SH3结构域，与CRK II有60%的同源性。在慢性粒细胞白血病中，CRKL是BCR/ABL癌蛋白的主要底物，可与BCR/ABL和c-ABL结合。已证明，在血小板生成素、促红细胞生成素或干细胞因子等配体介导的正常造血生长因子受体信号传导过程中，CRKL会发生酪氨酸磷酸化。此外，CRKL还参与由β整合素、B细胞或T细胞受体交联引发的信号传导。在结构上，CRKL的氨基末端SH3结构域已被证明可与C3G、SOS、PI3-K、c-ABL或BCR/ABL等蛋白质结合。CRKL的SH2结构域可与酪氨酸磷酸化的蛋白质如CBL、HEF1、CAS或桩蛋白结合。本综述总结了目前关于这种独特衔接蛋白在正常造血和白血病细胞信号传导中功能的认识。
