JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guesdon, F.
Right arrow Articles by Saklatvala, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guesdon, F.
Right arrow Articles by Saklatvala, J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Volume 272, Number 48, Issue of November 28, 1997 pp. 30017-30024
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Dual Specificity of the Interleukin 1- and Tumor Necrosis Factor-activated beta  Casein Kinase

(Received for publication, May 30, 1997, and in revised form, August 27, 1997)

François Guesdon , C. Graham Knight § , Lesley M. Rawlinson and Jeremy Saklatvala

From the  Kennedy Institute of Rheumatology, Hammersmith, London, W6 8LH, United Kingdom, the § Department of Cell Adhesion and Signaling, Strangeways Research Laboratory, Cambridge, CB1 4RN, United Kingdom, and the Division of Molecular and Genetic Medicine, Royal Hallamshire Hospital, Sheffield, S10 2JF, United Kingdom

Tumor necrosis factor (TNF) and interleukin 1 (IL1) activate a protein kinase, TIP kinase, which phosphorylates beta  casein in vitro. We have now identified its main phosphorylation site on beta  casein, Ser124 (Km approx  28 µM), and a minor phosphorylation site, Ser142 (Km approx  0.7 mM). The sequence motif that determined the phosphorylation of Ser124 by the kinase was studied with synthetic peptides bearing deletions or substitutions of the neighboring residues. This allowed synthesis of improved substrates (Km approx  6 µM) and showed that efficient phosphorylation of Ser124 was favored by the presence of large hydrophobic residues at positions +1, +9, +11, and +13 (counted relative to the position of the phosphoacceptor amino acid) and of a cysteine at position -2. Peptides in which Ser124 was replaced by tyrosine were also phosphorylated by TIP kinase, showing it to have dual specificity. It is unable to phosphorylate the MAP kinases in vitro and is therefore not directly involved in their activation. Its biochemical characteristics indicate that TIP kinase is a novel dual specificity kinase, perhaps related to the mixed lineage kinases. It copurified with a phosphoprotein of about 95 kDa, which could correspond either to the autophosphorylated kinase or to an associated substrate.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
J. Toshima, T. Tanaka, and K. Mizuno
Dual Specificity Protein Kinase Activity of Testis-specific Protein Kinase 1 and Its Regulation by Autophosphorylation of Serine-215 within the Activation Loop
J. Biol. Chem., April 23, 1999; 274(17): 12171 - 12176.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.