Maru Y, Peters K L, Afar D E, Shibuya M, Witte O N, Smithgall T E
Department of Genetics, University of Tokyo, Japan.
Mol Cell Biol. 1995 Feb;15(2):835-42. doi: 10.1128/MCB.15.2.835.
The human bcr gene encodes a protein with serine/threonine kinase activity, CDC24/dbl homology, a GAP domain, and an SH2-binding region. However, the precise physiological functions of BCR are unknown. Coexpression of BCR with the cytoplasmic protein-tyrosine kinase encoded by the c-fes proto-oncogene in Sf-9 cells resulted in stable BCR-FES protein complex formation and tyrosine phosphorylation of BCR. Association involves the SH2 domain of FES and a novel binding domain localized to the first 347 amino acids of the FES N-terminal region. Deletion of the homologous N-terminal BCR-binding domain from v-fps, a fes-related transforming oncogene, abolished transforming activity and tyrosine phosphorylation of BCR in vivo. Tyrosine phosphorylation of BCR in v-fps-transformed cells induced its association with GRB-2/SOS, the RAS guanine nucleotide exchange factor complex. These data provide evidence that BCR couples the cytoplasmic protein-tyrosine kinase and RAS signaling pathways.
人类bcr基因编码一种具有丝氨酸/苏氨酸激酶活性、CDC24/dbl同源性、GAP结构域和SH2结合区域的蛋白质。然而，BCR的确切生理功能尚不清楚。在Sf-9细胞中，BCR与由c-fes原癌基因编码的细胞质蛋白酪氨酸激酶共表达，导致稳定的BCR-FES蛋白复合物形成以及BCR的酪氨酸磷酸化。这种结合涉及FES的SH2结构域和定位于FES N端区域前347个氨基酸的一个新的结合结构域。从v-fps（一种与fes相关的转化癌基因）中缺失同源的N端BCR结合结构域，消除了体内的转化活性和BCR的酪氨酸磷酸化。v-fps转化细胞中BCR的酪氨酸磷酸化诱导其与GRB-2/SOS（RAS鸟嘌呤核苷酸交换因子复合物）结合。这些数据提供了证据，表明BCR将细胞质蛋白酪氨酸激酶和RAS信号通路联系起来。
