Rotational coupling of the transmembrane and kinase domains of the Neu receptor tyrosine kinase
Rotational coupling of the transmembrane and kinase domains of the Neu receptor tyrosine kinase
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DOI：
10.1091/mbc.11.10.3589
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发表时间：
2000-10-01
影响因子：
3.3
通讯作者：
Donoghue, DJ
中科院分区：
文献类型：
--
作者：
Bell, CA;Tynan, JA;Donoghue, DJ
配体与受体酪氨酸激酶（RTK）的结合调节受体二聚化和激酶结构域的活化。为了研究跨膜结构域在RTK激活调节中的作用，我们利用了简化的跨膜基序[VVVEVV]（n），其先前显示激活Neu受体。在这里，我们证明了跨膜结构域与激酶结构域的旋转连接，如Neu的周期性激活所证明的，因为二聚化基序在跨膜结构域上发生了转移。这些结果表明，激活需要激酶结构域相对于彼此的特定取向。血小板源性生长因子受体β的结果表明，这种跨膜结构域的激酶结构域的旋转连接可能是RTK的一般特征。这些观察结果表明，RTK跨膜和跨膜结构域中的激活突变将限于将激酶结构域定位在允许的旋转构象中的那些残基。
Ligand binding to receptor tyrosine kinases (RTKs) regulates receptor dimerization and activation of the kinase domain. To examine the role of the transmembrane domain in regulation of RTK activation, we have exploited a simplified transmembrane motif, [VVVEVVV](n), previously shown to activate the Neu receptor. Here we demonstrate rotational linkage of the transmembrane domain with the kinase domain, as evidenced by a periodic activation of Neu as the dimerization motif is shifted across the transmembrane domain. These results indicate that activation requires a specific orientation of the kinase domains with respect to each other. Results obtained with platelet-derived growth factor receptor-beta suggest that this rotational linkage of the transmembrane domain to the kinase domain may be a general feature of RTKs. These observations suggest hat activating mutations in RTK transmembrane and juxtamembrane domains will be limited to those residues that position the kinase domains in an allowed rotational conformation.