The protein kinase Cdk5

• DOI: 10.1046/j.1432-1327.2001.02024.x
• Publication Date: 2003-03-11T18:25:41Z
• Authors: Ricardo B. Maccioni; Carola Otth; Ilona I. Concha; Juan P. Muñoz
• Keywords: Cyclin-dependent kinase 5; ASK1; Cyclin-dependent kinase complex

A set of different protein kinases have been involved in tau phosphorylations, including glycogen synthase kinase 3β (GSK3β), MARK kinase, MAP the cyclin‐dependent 5 (Cdk5) system and others. The latter include catalytic component Cdk5 regulatory proteins p35, p25 p39. its neuron‐specific activator p35 are essential molecules for neuronal migration laminar configuration cerebral cortex. Recent evidence that Cdk5/p35 complex concentrates at leading edge axonal growth cones, together with involvement this phosphorylation microtubule‐asociated (MAPs), provide further support to role regulating extension developing brain neurons. Although aminoacid sequence has little similarity those normal cyclins, studies shown activation domain may adopt a conformation cyclin‐folded structure. computed structure is compatible experimental data obtained from on complex, allowed predictions interacting domains. This enzyme exhibits wide cell distribution, even though regulated activity only cells. characterized as proline‐directed Ser/Thr contributes human Ser202, Thr205, Ser235 Ser404. active postmitiotic neurons, it implicated cytoskeleton assembly organization during growth. In addition other MAPs, phosphorylates high molecular weight neurofilament their C‐terminal domain. Moreover, nestin, regulates muscular cells development early embryos, several appear be substrates phosphorylated by kinase. Studies also suggest, differentiation, induced myogenesis, however, mechanisms how differentiation not yet elucidated. β‐amyloid peptide (Aβ) induces deregulation cultured cells, raises question possible roles tau‐phosphorylating events death triggered Aβ. context, there hyperphosphorylation promoted Aβ fibrillary form. inhibitors protect hippocampal neurons against both anomalous phosphorylations death. links between neurogenesis claimed participation neurodegeneration, framework understand relevance system, changes regulation disturbances such occurring Alzheimer disease.