Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth.
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.
Zukerberg
L R
LR
Howard Hughes Medical Institute, Department of Pathology, Massachusetts General Hospital, Boston 02114, USA.
Patrick
G N
GN
Nikolic
M
M
Humbert
S
S
Wu
C L
CL
Lanier
L M
LM
Gertler
F B
FB
Vidal
M
M
Van Etten
R A
RA
Tsai
L H
LH
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
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