Ca2+ /S100 regulation of giant protein kinases

Heierhorst, Jörg, Kobe, Bostjan, Feil, Susanne C., Parker, Michael W., Benian, Guy M., Weiss, Klaudiusz R. and Kemp, Bruce E. (1996) Ca2+ /S100 regulation of giant protein kinases. Nature, 380 6575: 636-639. doi:10.1038/380636a0


Author Heierhorst, Jörg
Kobe, Bostjan
Feil, Susanne C.
Parker, Michael W.
Benian, Guy M.
Weiss, Klaudiusz R.
Kemp, Bruce E.
Title Ca2+ /S100 regulation of giant protein kinases
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
1476-4687
Publication date 1996-04-01
Year available 1996
Sub-type Article (original research)
DOI 10.1038/380636a0
Open Access Status Not yet assessed
Volume 380
Issue 6575
Start page 636
End page 639
Total pages 4
Place of publication London, UK
Publisher Nature Publishing Group
Language eng
Subject 060111 Signal Transduction
Abstract Protein phosphorylation by protein kinases plays a central regulatory role in cellular processes and these kinases are themselves tightly regulated(1). One common mechanism of regulation involves Ca2+-binding proteins (CaBP) such as calmodulin (CaM)(2). Here we report a Ca2+-effector mechanism for protein kinase activation by demonstrating the specific and >1,000-fold activation of the myosin-associated giant protein kinase twitchin by Ca2+/S100A1(2). S100A1(2) is a member of a large CaBP family that is implicated in various cellular processes, including cell growth, differentiation and motility, but whose molecular actions are largely unknown(3). The S100A1(2)-binding site is a part of the autoregulatory sequence positioned in the active site that is responsible for intrasteric autoinhibition of twitchin kinase; the mechanism of autoinhibition based on the crystal structures of two twitchin kinase fragments is described elsewhere(4). Ca2+/S100 represents a likely physiological activator for the entire family of giant protein kinases involved in muscle contractions and cytoskeletal structure(2,5-9).
Formatted abstract
PROTEIN phosphorylation by protein kinases plays a central regulatory role in cellular processes and these kinases are themselves tightly regulated1. One common mechanism of regulation involves Ca2+-binding proteins (CaBP) such as calmodu-lin (CaM)2. Here we report a Ca2+-effector mechanism for protein kinase activation by demonstrating the specific and > 1,000-fold activation of the myosin-associated giant protein kinase twitchin by Ca2+/S100Al2. S100A12 is a member of a large CaBP family that is implicated in various cellular processes, including cell growth, differentiation and motility, but whose molecular actions are largely unknown3. The S100Al2-binding site is a part of the autoregulatory sequence positioned in the active site that is responsible for intrasteric autoinhibition of twitchin kinase; the mechanism of autoinhibition based on the crystal structures of two twitchin kinase fragments is described elsewhere4. Ca2+/S100 represents a likely physiological activator for the entire family of giant protein kinases involved in muscle contractions and cyto-skeletal structure2,5–9.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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