title: Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Zukerberg
authors.forename: G N
authors.initials: GN
authors.lastname: Patrick
authors.forename: M
authors.initials: M
authors.lastname: Nikolic
authors.forename: S
authors.initials: S
authors.lastname: Humbert
authors.forename: C L
authors.initials: CL
authors.lastname: Wu
authors.forename: L M
authors.initials: LM
authors.lastname: Lanier
authors.forename: F B
authors.initials: FB
authors.lastname: Gertler
authors.forename: M
authors.initials: M
authors.lastname: Vidal
authors.forename: R A
authors.initials: RA
authors.lastname: Van Etten
authors.forename: L H
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000502:physiology*; D016213:Cyclins; D004622:Embryo, Mammalian; D051379:Mice; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C411580:Cables1 protein, mouse; D002352:Carrier Proteins; D016213:Cyclins; D010750:Phosphoproteins; D014443:Tyrosine; D010770:Phosphotransferases; D016315:Proto-Oncogene Proteins c-abl; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases