Tyrosine Phosphorylation of Dbl Regulates GTPase Signaling
Tyrosine Phosphorylation of Dbl Regulates GTPase Signaling
复制标题
DOI：
10.1074/jbc.m114.573782
复制
发表时间：
2014-06-13
影响因子：
4.8
通讯作者：
Manor, Danny
中科院分区：
文献类型：
--
作者：
Gupta, Meghana;Qi, Xiaojun;Manor, Danny
Rho GTP酶是一种分子“开关”，在“开”(GTP结合)和“关”(GDP结合)之间循环，调节许多细胞活动，如基因表达、蛋白质合成、细胞骨架重排和代谢反应。GTP酶调节失调是许多疾病的一个重要特征，尤其是癌症。DBL家族的鸟嘌呤核苷酸交换因子(GEF)被有丝分裂的细胞表面受体激活，并激活Rho家族的GTP酶CDc42、rac1和RhoA。DBL家族中调节GEF的分子机制还知之甚少。我们的研究表明，在生长因子的刺激下，DBL在酪氨酸残基上被磷酸化，这一事件对于全球环境基金的调节激活至关重要。这些发现揭示了这种蛋白质生理调节的一层新的复杂性。
Rho GTPases are molecular "switches" that cycle between "on" (GTP-bound) and "off" (GDP-bound) states and regulate numerous cellular activities such as gene expression, protein synthesis, cytoskeletal rearrangements, and metabolic responses. Dysregulation of GTPases is a key feature of many diseases, especially cancers. Guanine nucleotide exchange factors (GEFs) of the Dbl family are activated by mitogenic cell surface receptors and activate the Rho family GTPases Cdc42, Rac1, and RhoA. The molecular mechanisms that regulate GEFs from the Dbl family are poorly understood. Our studies reveal that Dbl is phosphorylated on tyrosine residues upon stimulation by growth factors and that this event is critical for the regulated activation of the GEF. These findings uncover a novel layer of complexity in the physiological regulation of this protein.