原癌基因酪氨酸蛋白激酶Src
SH3域
SH2域
酪氨酸激酶
化学
细胞生物学
磷酸酪氨酸结合域
Src家族激酶
表皮生长因子
酪氨酸
磷酸化
信号转导
生物化学
生物
受体
作者
Metta Dülk,Bálint Szeder,Gábor Glatz,Balázs Merő,Kitti Koprivanacz,Gyöngyi Kudlik,Virág Vas,Szabolcs Sipeki,Anna Cserkaszky,László Radnai,László Buday
出处
期刊:Biochemistry
[American Chemical Society]
日期:2018-06-21
卷期号:57 (28): 4186-4196
被引量:22
标识
DOI:10.1021/acs.biochem.8b00084
摘要
The nonreceptor tyrosine kinase Src is a central component of the epidermal growth factor (EGF) signaling pathway. Our group recently showed that the Frank-ter Haar syndrome protein Tks4 (tyrosine kinase substrate with four Src homology 3 domains) is also involved in EGF signaling. Here we demonstrate that Tks4 and Src bind directly to each other and elucidate the details of the molecular mechanism of this complex formation. Results of GST pull-down and fluorescence polarization assays show that both a proline-rich SH3 binding motif (PSRPLPDAP, residues 466–474) and an adjacent phosphotyrosine-containing SH2 binding motif (pYEEI, residues 508–511) in Tks4 are responsible for Src binding. These motifs interact with the SH3 and SH2 domains of Src, respectively, leading to a synergistic enhancement of binding strength and a highly stable, "bidentate"-type of interaction. In agreement with these results, we found that the association of Src with Tks4 is permanent and the complex lasts at least 3 h in living cells. We conclude that the interaction of Tks4 with Src may result in the long term stabilization of the kinase in its active conformation, leading to prolonged Src activity following EGF stimulation.
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