Hello Rahul, it might appear that cdk5 follows a regulatory mechanism similar to other cdk kinases; movement of the T loop towards the kinase C lobe as a result of interaction between the phosphate and some acidic residues, and the opening of the catalytic clef thereby increasing the kinase activity. Article Regulation of cdk5 catalytic activity by phosphorylation

Article Cdk5 activity in the brain - multiple paths of regulation

Thank you Maurice

HiRahul Singh

I agree with Maurice Ekpenyong

regard

Small molecule inhibitors of CDK5 protect neurons from cell death following various insults. Investigated that changes in protein phosphorylation in cultured rat cerebellar granule neurons after administration of the CDK5 inhibitor Indolinone A. By immunoblot analysis detected that enhanced phosphorylation of the extracellular signal-regulated kinase1/2 (ERK1/2) and the Jun N-terminal kinase (JNK) substrate c-Jun. Co-administration of U0126, an inhibitor of ERK1/2, or SP600125, an inhibitor of JNK, blocked phosphorylation of ERK1/2 or c-Jun, but did not affect neuroprotection by the CDK5 inhibitor. By metal affinity chromatography, two-dimensional (2D) gel electrophoresis, and MALDI-TOF mass spectrometry identified several phosphoproteins that accumulated in neurons treated with Indolinone A. Among them were proteins involved in neurotransmitter release, which is consistent with a physiological function of CDK5 in synaptic signaling. Moreover, identified that proteins acting in energy metabolism, protein folding, and oxidative stress response. Similar findings have been reported in yeast following inhibition of Pho85 kinase, which is homologous to mammalian CDK5 and acts in environmental stress signaling. These results suggest that inhibition of CDK5 activates stress responsive proteins that may protect neurons against subsequent injurious stimulation.

Hope this info will help you.

Good luck!