Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth

Lawrence R. Zukerberg; Gentry N. Patrick; Margareta Nikolic; Sandrine Humbert; Chin Lee Wu; Lorene M. Lanier; Frank B. Gertler; Marc Vidal; Richard A. Van Etten; Li Huei Tsai

doi:10.1016/S0896-6273(00)81200-3

Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth

Lawrence R. Zukerberg, Gentry N. Patrick, Margareta Nikolic, Sandrine Humbert, Chin Lee Wu, Lorene M. Lanier, Frank B. Gertler, Marc Vidal, Richard A. Van Etten, Li Huei Tsai

Neuroscience

Research output: Contribution to journal › Article › peer-review

336 Scopus citations

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.

Original language	English (US)
Pages (from-to)	633-646
Number of pages	14
Journal	Neuron
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/S0896-6273(00)81200-3
State	Published - 2000

Bibliographical note

Funding Information:
The authors would like to thank Yolande Ramos and Shih-Te Wen for DNA constructs and technical support; Ming Sum Lee, Vivien Tannoch, Young Kwon, Deanna Smith, and Elena Porro for help in preparation of this manuscript; and members of the Tsai laboratory for helpful discussions. L. Lanier is supported by the Anna Fuller Fund, and F. Gertler is supported by Merck and Company. This work was supported in part by National Institutes of Health grant RO1-NS37007 (to L.-H. T.). L.-H. T. is an assistant investigator of the Howard Hughes Medical Institute, a Rita Allen Foundation scholar, and a recipient of an Esther A. and Joseph Klingenstein Foundation Fund.

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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.",

author = "Zukerberg, {Lawrence R.} and Patrick, {Gentry N.} and Margareta Nikolic and Sandrine Humbert and Wu, {Chin Lee} and Lanier, {Lorene M.} and Gertler, {Frank B.} and Marc Vidal and {Van Etten}, {Richard A.} and Tsai, {Li Huei}",

note = "Funding Information: The authors would like to thank Yolande Ramos and Shih-Te Wen for DNA constructs and technical support; Ming Sum Lee, Vivien Tannoch, Young Kwon, Deanna Smith, and Elena Porro for help in preparation of this manuscript; and members of the Tsai laboratory for helpful discussions. L. Lanier is supported by the Anna Fuller Fund, and F. Gertler is supported by Merck and Company. This work was supported in part by National Institutes of Health grant RO1-NS37007 (to L.-H. T.). L.-H. T. is an assistant investigator of the Howard Hughes Medical Institute, a Rita Allen Foundation scholar, and a recipient of an Esther A. and Joseph Klingenstein Foundation Fund. ",

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AU - Zukerberg, Lawrence R.

AU - Patrick, Gentry N.

AU - Nikolic, Margareta

AU - Humbert, Sandrine

AU - Wu, Chin Lee

AU - Lanier, Lorene M.

AU - Gertler, Frank B.

AU - Vidal, Marc

AU - Van Etten, Richard A.

AU - Tsai, Li Huei

N1 - Funding Information: The authors would like to thank Yolande Ramos and Shih-Te Wen for DNA constructs and technical support; Ming Sum Lee, Vivien Tannoch, Young Kwon, Deanna Smith, and Elena Porro for help in preparation of this manuscript; and members of the Tsai laboratory for helpful discussions. L. Lanier is supported by the Anna Fuller Fund, and F. Gertler is supported by Merck and Company. This work was supported in part by National Institutes of Health grant RO1-NS37007 (to L.-H. T.). L.-H. T. is an assistant investigator of the Howard Hughes Medical Institute, a Rita Allen Foundation scholar, and a recipient of an Esther A. and Joseph Klingenstein Foundation Fund.

PY - 2000

Y1 - 2000

N2 - 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.

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Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth

Abstract

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