Figure 6.
CDK5 phosphorylation substrates during neuronal migration. When CDK5 is activated by binding of CDK5R1 (p35)/CDK5R2 (p39), this kinase phosphorylates multiple substrates in migrating neurons. Among those substrates, DCX, NDEL1, MTAP1B and PTK2 (FAK) are MT-regulating proteins. A very interesting phosphorylation substrate of CDK5 is CDKN1B (p27kip1). P-CDKN1B suppresses RHOA GTPase activity. RHOA-ROCK-LIMK1-CFL1 and RHOA-ROCK-MLC signaling pathway have been implicated in actin cytoskeletal remodeling during neuronal migration. CDK5 indirectly affects these actin-regulating signaling pathways by modulating CDK5N1B function. (Blue proteins: MT regulators, red proteins: actin regulators)