Sharma Monica, Hanchate Naresh Kumar, Tyagi Rakesh K, Sharma Pushkar
Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.
Biochem Biophys Res Commun. 2007 Jun 29;358(2):379-84. doi: 10.1016/j.bbrc.2007.04.149. Epub 2007 May 4.
Cyclin dependent kinase 5 (cdk5) is active mainly in postmitotic cells like neurons and regulates important cellular functions by phosphorylating a wide variety of targets. Nerve growth factor stimulates the MEK-ERK MAP kinase pathway and causes neuronal differentiation and survival. It was reported previously that Cdk5 inhibits the MAP kinase pathway by phosphorylating Map kinase kinase-1 (MEK1) [1]. We have delineated the functional consequence of this cross talk and found that the cdk5 mediated inhibition of MEK1 results in apoptosis. We also demonstrate that the activity of transcription factor CREB, which is known to play pro-survival roles in neuronal cells, is attenuated as a result of this cross-talk.
细胞周期蛋白依赖性激酶5（cdk5）主要在诸如神经元等有丝分裂后细胞中具有活性，并通过磷酸化多种靶标来调节重要的细胞功能。神经生长因子刺激MEK-ERK丝裂原活化蛋白激酶途径并导致神经元分化和存活。先前有报道称，Cdk5通过磷酸化丝裂原活化蛋白激酶激酶-1（MEK1）来抑制丝裂原活化蛋白激酶途径[1]。我们已经阐明了这种相互作用的功能后果，发现cdk5介导的对MEK1的抑制会导致细胞凋亡。我们还证明，已知在神经元细胞中发挥促存活作用的转录因子CREB的活性，由于这种相互作用而减弱。
