Universität zu Köln

Hagmann, Henning, Taniguchi, Yoshinori, Pippin, Jeffrey W., Kauerz, Hans-Michael, Benzing, Thomas, Shankland, Stuart J. and Brinkkoetter, Paul Thomas (2015). Cyclin I and p35 determine the subcellular distribution of Cdk5. Am. J. Physiol.-Cell Physiol., 308 (4). S. C339 - 9. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1563

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Abstract

The atypical cyclin-dependent kinase 5 (Cdk5) serves an array of different functions in cell biology. Among these are axonal guidance, regulation of intercellular contacts, cell differentiation, and prosurvival signaling. The variance of these functions suggests that Cdk5 activation comes to pass in different cellular compartments. The kinase activity, half-life, and substrate specificity of Cdk5 largely depend on specific activators, such as p25, p35, p39, and cyclin I. We hypothesized that the subcellular distribution of Cdk5 activators also determines the localization of the Cdk5 protein and sets the stage for targeted kinase activity within distinct cellular compartments to suit the varying roles of Cdk5. Cdk5 localization was analyzed in murine kidney and brain slices of wild-type and cyclin I- and/or p35-null mice by immunohistochemistry and in cultured mouse podocytes using immunofluorescence labeling, as well as cell fractionation experiments. The predominance of cyclin I mediates the nuclear localization of Cdk5, whereas the predominance of p35 results in a membranous localization of Cdk5. These findings were further substantiated by overexpression of cyclin I and p35 with altered targeting characteristics in human embryonic kidney 293T cells. These studies reveal that the subcellular localization of Cdk5 is determined by its specific activators. This results in the directed Cdk5 kinase activity in specific cellular compartments dependent on the activator present and allows Cdk5 to serve multiple independent roles.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Taniguchi, Yoshinori UNSPECIFIED UNSPECIFIED UNSPECIFIED Pippin, Jeffrey W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kauerz, Hans-Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Shankland, Stuart J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Paul Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-407601
DOI:	10.1152/ajpcell.00168.2014
Journal or Publication Title:	Am. J. Physiol.-Cell Physiol.
Volume:	308
Number:	4
Page Range:	S. C339 - 9
Date:	2015
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1563
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DETERGENT-RESISTANT MEMBRANES; DEPENDENT KINASE-5 CDK5; FC-EPSILON-RI; NUCLEAR-LOCALIZATION; TAU-PHOSPHORYLATION; PROTECTS PODOCYTES; STRUCTURAL ASPECTS; SLIT DIAPHRAGM; BOVINE BRAIN; APOPTOSIS Multiple languages Cell Biology; Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40760