Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on December 16, 2005
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
280/50/41675    most recent
M510711200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bullock, A. N.
Right arrow Articles by Turk, B. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bullock, A. N.
Right arrow Articles by Turk, B. E.
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?

Papers In Press, published online ahead of print October 13, 2005
J. Biol. Chem, 10.1074/jbc.M510711200
Submitted on September 30, 2005
Revised on October 12, 2005
Accepted on October 13, 2005

Structure and substrate specificity of the Pim-1 kinase

Alex N. Bullock, Judit Debreczeni, Ann Amos, Stefan Knapp, and Benjamin E. Turk

Pharmacology Dept., Yale University School of Medicine, New Haven, CT 06520

Corresponding Author: ben.turk{at}yale.edu

The Pim kinases are a family of three vertebrate protein serine/threonine kinases (Pim-1, 2 and 3) belonging to the CAMK (calmodulin-dependent protein kinase-related) group. Pim kinases are emerging as important mediators of cytokine signaling pathways in hematopoietic cells, and contribute to the progression of certain leukemias and solid tumors. A number of cytoplasmic and nuclear proteins are phosphorylated by Pim kinases and may act as their effectors in normal physiology and in disease. Recent crystallographic studies of Pim-1 have identified unique structural features but have not provided insight into how the kinase recognizes its target substrates. Here, we have conducted peptide library screens to exhaustively determine the sequence specificity of active site-mediated phosphorylation by Pim-1 and Pim-3. We have identified the major site of Pim-1 autophosphorylation and find surprisingly that it maps to a novel site that diverges from its consensus phosphorylation motif. We have solved the crystal structure of Pim-1 bound to a high affinity peptide substrate in complexes with either the ATP analogue AMP-PNP or the bisindolyl-maleimide kinase inhibitor BIM1. These structures reveal an unanticipated mode of recognition for basic residues upstream of the phosphorylation site, distinct from that of other kinases with similar substrate specificity. The structures provide a rationale for the unusually high affinity of Pim kinases for peptide substrates and suggest a general mode for substrate binding to members of the CAMK group.


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
 BloodHome page
S. A. Didichenko, N. Spiegl, T. Brunner, and C. A. Dahinden
IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils
Blood, November 15, 2008; 112(10): 3949 - 3958.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. Morishita, R. Katayama, K. Sekimizu, T. Tsuruo, and N. Fujita
Pim Kinases Promote Cell Cycle Progression by Phosphorylating and Down-regulating p27Kip1 at the Transcriptional and Posttranscriptional Levels
Cancer Res., July 1, 2008; 68(13): 5076 - 5085.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
V. Pogacic, A. N. Bullock, O. Fedorov, P. Filippakopoulos, C. Gasser, A. Biondi, S. Meyer-Monard, S. Knapp, and J. Schwaller
Structural Analysis Identifies Imidazo[1,2-b]Pyridazines as PIM Kinase Inhibitors with In vitro Antileukemic Activity
Cancer Res., July 15, 2007; 67(14): 6916 - 6924.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
U. E. E. Rennefahrt, S. W. Deacon, S. A. Parker, K. Devarajan, A. Beeser, J. Chernoff, S. Knapp, B. E. Turk, and J. R. Peterson
Specificity Profiling of Pak Kinases Allows Identification of Novel Phosphorylation Sites
J. Biol. Chem., May 25, 2007; 282(21): 15667 - 15678.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
C. Peng, A. Knebel, N. A. Morrice, X. Li, K. Barringer, J. Li, S. Jakes, B. Werneburg, and L. Wang
Pim Kinase Substrate Identification and Specificity
J. Biochem., March 1, 2007; 141(3): 353 - 362.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
S. Holder, M. Zemskova, C. Zhang, M. Tabrizizad, R. Bremer, J. W. Neidigh, and M. B. Lilly
Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase
Mol. Cancer Ther., January 1, 2007; 6(1): 163 - 172.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y.-Y. Li, B. K. Popivanova, Y. Nagai, H. Ishikura, C. Fujii, and N. Mukaida
Pim-3, a Proto-Oncogene with Serine/Threonine Kinase Activity, Is Aberrantly Expressed in Human Pancreatic Cancer and Phosphorylates Bad to Block Bad-Mediated Apoptosis in Human Pancreatic Cancer Cell Lines.
Cancer Res., July 1, 2006; 66(13): 6741 - 6747.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement