Zukerberg L R, Patrick G N, Nikolic M, Humbert S, Wu C L, Lanier L M, Gertler F B, Vidal M, Van Etten R A, Tsai L H
Howard Hughes Medical Institute, Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
Neuron. 2000 Jun;26(3):633-46. doi: 10.1016/s0896-6273(00)81200-3.
Cyclin-dependent kinase 5 (Cdk5) is a small serine/threonine kinase that plays a pivotal role during development of the CNS. Cables, a novel protein, interacts with Cdk5 in brain lysates. Cables also binds to and is a substrate of the c-Abl tyrosine kinase. Active c-Abl kinase leads to Cdk5 tyrosine phosphorylation, and this phosphorylation is enhanced by Cables. Phosphorylation of Cdk5 by c-Abl occurs on tyrosine 15 (Y15), which is stimulatory for p35/Cdk5 kinase activity. Expression of antisense Cables in primary cortical neurons inhibited neurite outgrowth. Furthermore, expression of active Abl resulted in lengthening of neurites. The data provide evidence for a Cables-mediated interplay between the Cdk5 and c-Abl signaling pathways in the developing nervous system.
细胞周期蛋白依赖性激酶5（Cdk5）是一种小的丝氨酸/苏氨酸激酶，在中枢神经系统发育过程中起关键作用。Cables是一种新型蛋白质，可与脑裂解物中的Cdk5相互作用。Cables还与c-Abl酪氨酸激酶结合并作为其底物。活性c-Abl激酶导致Cdk5酪氨酸磷酸化，并且这种磷酸化被Cables增强。c-Abl对Cdk5的磷酸化发生在酪氨酸15（Y15）上，这对p35/Cdk5激酶活性具有刺激作用。在原代皮层神经元中反义Cables的表达抑制了神经突生长。此外，活性Abl的表达导致神经突延长。这些数据为发育中的神经系统中Cables介导的Cdk5和c-Abl信号通路之间的相互作用提供了证据。
