Interaction and functional cooperation between the serine/threonine kinase bone morphogenetic protein type II receptor with the tyrosine kinase stem cell factor receptor
Interaction and functional cooperation between the serine/threonine kinase bone morphogenetic protein type II receptor with the tyrosine kinase stem cell factor receptor
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DOI：
10.1002/jcp.20480
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发表时间：
2006-02-01
影响因子：
5.6
通讯作者：
Souchelnytskyi, S
中科院分区：
文献类型：
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作者：
Hassel, S;Yakymovych, M;Souchelnytskyi, S
具有内在丝氨酸/苏氨酸或酪氨酸激酶结构域的跨膜受体调节多细胞真核生物中细胞的重要功能，例如分化、凋亡和增殖。在此，我们证明具有丝氨酸/苏氨酸激酶结构域的骨形成蛋白II型受体（BMPR-II）和含有酪氨酸激酶结构域的干细胞因子受体（c-kit）在体外和体内形成复合物；用 BMP2 和 SCF 处理细胞时会诱导相互作用。干细胞因子 (SCF) 调节 BMP2 依赖性 Smad1/5/8 激活和 Erk 激酶磷酸化。 SCF 还增强了 C2C12 细胞的 BMP2 依赖性分化。我们发现 BMPR-II 在与 c-kit 共表达并激活后在 Ser757 处被磷酸化。 BMPR-II 磷酸化需要 BMPR-II 的完整激酶活性。取消 BMPR-II Ser757 处的 c-kit/SCF 依赖性磷酸化会干扰 BMP2 和 SCF 的协同作用。我们的数据表明，c-kit 和 BMPR-II 之间的复合物形成导致 BMPR-II Ser757 磷酸化，从而调节 BMPR-II 依赖性信号传导。
Transmembrane receptors with intrinsic serine/threonine or tyrosine kinase domains regulate vital functions of cells in multicellular eukaryotes, e.g., differentiation, apoptosis, and proliferation. Here, we show that bone rnorphogenetic protein type II receptor (BMPR-II)which has a serine/threonine kinase domain, and stem cell factor receptor (c-kit) which contains a tyrosine kinase domain form a complex in vitro and in vivo; the interaction is induced upon treatment of cells with BMP2 and SCF. Stem cell factor (SCF) modulated BMP2-dependent activation of Smad1/5/8 and phosphorylation of Erk kinase. SCF also enhanced BMP2-dependent differentiation of C2C12 cells. We found that BMPR-II was phosphorylated at Ser757 upon co-expression with and activation of c-kit. BMPR-II phosphorylation required intact kinase activity of BMPR-II. Abrogation of the c-kit/SCF-dependent phosphorylation of BMPR-II at the Ser757 interfered with the cooperative effect of BMP2 and SCF. Our data suggest that the complex formation between c-kit and BMPR-II leads to phosphorylation of BMPR-II at Ser757, which modulates BMPR-II-dependent signaling.