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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence / genetics
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Animals
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Base Sequence / genetics
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COS Cells
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cells, Cultured
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / metabolism
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Cyclin-Dependent Kinases / physiology*
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Cyclins*
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Embryo, Mammalian
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Mice
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Mitosis / physiology
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Molecular Sequence Data
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Neurites / physiology*
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Neurons / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Phosphoproteins / physiology*
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Phosphorylation
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Phosphotransferases / metabolism*
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Proto-Oncogene Proteins c-abl / physiology*
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Substrate Specificity
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Tyrosine / metabolism
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Up-Regulation
Substances
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Cables1 protein, mouse
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Carrier Proteins
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Cyclins
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Phosphoproteins
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Tyrosine
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Phosphotransferases
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Proto-Oncogene Proteins c-abl
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Cyclin-Dependent Kinase 5
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Cdk5 protein, mouse
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Cyclin-Dependent Kinases