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首页> 外文期刊>Molecular and Cellular Biology >Deciphering the Cross Talk between hnRNP K and c-Src: the c-Src Activation Domain in hnRNP K Is Distinct from a Second Interaction Site
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Deciphering the Cross Talk between hnRNP K and c-Src: the c-Src Activation Domain in hnRNP K Is Distinct from a Second Interaction Site

机译:解密hnRNP K和c-Src之间的串扰:hnRNP K中的c-Src激活域与第二个相互作用位点不同

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The protein tyrosine kinase c-Src is regulated by two intramolecular interactions. The repressed state is achieved through the interaction of the Src homology 2 (SH2) domain with the phosphorylated C-terminal tail and the association of the SH3 domain with a polyproline type II helix formed by the linker region between SH2 and the kinase domain. hnRNP K, the founding member of the KH domain protein family, is involved in chromatin remodeling, regulation of transcription, and translation of specific mRNAs and is a target in different signal transduction pathways. In particular, it functions as a specific activator and a substrate of the tyrosine kinase c-Src. Here we address the question how hnRNP K interacts with and activates c-Src. We define the proline residues in hnRNP K in the proline-rich motifs P2 (amino acids [aa] 285 to 297) and P3 (aa 303 to 318), which are necessary and sufficient for the specific activation of c-Src, and we dissect the amino acid sequence (aa 216 to 226) of hnRNP K that mediates a second interaction with c-Src. Our findings indicate that the interaction with c-Src and the activation of the kinase are separable functions of hnRNP K. hnRNP K acts as a scaffold protein that integrates signaling cascades by facilitating the cross talk between kinases and factors that mediate nucleic acid-directed processes.
机译:蛋白质酪氨酸激酶c-Src受两个分子内相互作用调节。通过Src同源性2(SH2)域与磷酸化的C末端尾巴的相互作用以及SH3域与由SH2和激酶域之间的连接区形成的聚脯氨酸II型螺旋的缔合,可​​以实现抑制状态。 hnRNP K是KH域蛋白家族的创始成员,参与染色质重塑,转录调控和特定mRNA的翻译,并且是不同信号转导途径的靶标。特别地,其充当酪氨酸激酶c-Src的特异性活化剂和底物。在这里,我们解决hnRNP K如何与c-Src相互作用并激活c-Src的问题。我们在富含脯氨酸的基序P2(氨基酸[aa] 285至297)和P3(aa 303至318)中定义了hnRNP K中的脯氨酸残基,这些残基对于c-Src的特异性激活是必需的,并且足够解析hnRNP K的氨基酸序列(aa 216至226),该序列介导与c-Src的第二次相互作用。我们的发现表明与c-Src的相互作用和激酶的激活是hnRNP K的可分离功能。hnRNP K充当支架蛋白,通过促进激酶与介导核酸定向过程的因子之间的相互干扰,整合信号级联。 。

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