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PMID: 9774336 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins.

The EMBO journal ·Vol. 17 ·No. 20 ·1998-10-15 ·Pages 5913-22

Millward TA, Heizmann CW, Schäfer BW, Hemmings BA

Abstract

Ndr is a nuclear serine/threonine protein kinase that belongs to a subfamily of kinases identified as being critical for the regulation of cell division and cell morphology. The regulatory mechanisms that control Ndr activity have not been characterized previously. In this paper, we present evidence that Ndr is regulated by EF-hand calcium-binding proteins of the S100 family, in response to changes in the intracellular calcium concentration. In vitro, S100B binds directly to and activates Ndr in a Ca2+-dependent manner. Moreover, Ndr is recovered from cell lysates in anti-S100B immunoprecipitates. The region of Ndr responsible for interaction with Ca2+/S100B is a basic/hydrophobic motif within the N-terminal regulatory domain of Ndr, and activation of Ndr by Ca2+/S100B is inhibited by a synthetic peptide derived from this region. In cultured cells, Ndr is rapidly activated following treatment with Ca2+ ionophore, and this activation is dependent upon the identified Ca2+/S100B-binding domain. Finally, Ndr activity is inhibited by W-7 in melanoma cells overexpressing S100B, but is unaffected by W-7 in melanoma cells that lack S100B. These results suggest that Ndr is regulated at least in part by changes in the intracellular calcium concentration, through binding of S100 proteins to its N-terminal regulatory domain.

MeSH Terms
Animals COS Cells Calcium/physiology Calcium Signaling/physiology Calcium-Binding Proteins/physiology Cell Nucleus/enzymology Cells, Cultured Enzyme Activation Humans Nerve Growth Factors/physiology Phosphorylation Protein Binding Protein Serine-Threonine Kinases/metabolism S100 Calcium Binding Protein beta Subunit S100 Proteins
Chemicals
Calcium-Binding Proteins Nerve Growth Factors S100 Calcium Binding Protein beta Subunit S100 Proteins S100B protein, human Protein Serine-Threonine Kinases Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Millward T A
Friedrich Miescher-Institut, Maulbeerstrasse 66, CH-4058 Basel.
Heizmann C W
Schäfer B W
Hemmings B A
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.20.5913
Published
1998-10-15
Pages
5913-22
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170919
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/17.20.5913 PMC Full Text View journal details
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