Document Detail

Posttranslational regulation of Lck and a p36-38 protein by activators of protein kinase C: differential effects of the tumor promoter, PMA, and the non-tumor-promoter, bryostatin.
MedLine Citation:
PMID:  9225005     Owner:  NLM     Status:  MEDLINE    
T cell activation via the antigen receptor or by PKC-activating drugs results in phosphorylation of Lck and alteration of its electrophoretic mobility. Although tyrosine phosphorylation appears to regulate Lck enzymatic activity, the significance of phosphorylation of serine residues and its relevance to the cell proliferation process are yet unclear. We found that the PKC activator, bryostatin, like PMA, induced the conversion of p56lck to a slower migrating form with an apparent molecular mass of 60 kDa. The effect of PMA lasted over 48 hr but that of bryostatin was transient and correlated in time kinetics with that of the bryostatin-induced degradation of PKC. The effects of bryostatin were dominant over those of PMA. In addition, PKC was found to affect both serine and tyrosine phosphorylation of Lck but had no significant effect on the in vitro catalytic activity of Lck. To test whether serine phosphorylation of Lck may affect its ability to bind tyrosine phosphoproteins, we compared Lck immunoprecipitates from PMA- and bryostatin-treated T cells. We found that a 36- to 38-kDa tyrosine phosphoprotein co-immunoprecipitated with Lck from cells that were treated for 24 hr with PMA, but not bryostatin. A p36-38 from PMA- but not bryostatin-treated cells also interacted with an Lck-SH2 fusion protein, suggesting differential regulation of p36-38 by PMA and bryostatin. Furthermore, in vitro phosphorylation of p36-38 occurred in lysates of cells that were treated for 24 hr with PMA, but not in lysates of bryostatin-treated cells. The results show that tyrosine phosphorylation and the association of p36-38 with Lck are differentially affected by bryostatin and PMA and suggest that PKC regulates the interaction of potential signaling molecules with Lck, thereby regulating biochemical events that are relevant to T cell mitogenesis and/or transformation.
D Galron; I J Ansotegui; N Isakov
Related Documents :
3196805 - Stimulatory effect of phorbol diester on relaxin release by porcine luteal cells in cul...
17013755 - Lymph node cells from balb/c mice with chronic visceral leishmaniasis exhibiting cellul...
12525665 - Protein phosphatase 2a enhances activation of human immunodeficiency virus type 1 by ph...
1910305 - Cellular mechanism of synergistic stimulation of pge2 production by phorbol diester and...
22496355 - Arsenic trioxide induces abnormal mitotic spindles through a pip4kiiγ/rho pathway.
19088455 - Phosphatidylinositide dependent kinase deficiency increases anxiety and decreases gaba ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular immunology     Volume:  178     ISSN:  0008-8749     ISO Abbreviation:  Cell. Immunol.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-08-08     Completed Date:  1997-08-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  141-51     Citation Subset:  IM    
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adjuvants, Immunologic / pharmacology
Carcinogens / pharmacology*
Electrophoresis, Polyacrylamide Gel
Enzyme Activation
Lactones / pharmacology*
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Molecular Weight
Phosphoproteins / metabolism
Phosphoserine / metabolism
Phosphothreonine / metabolism
Phosphotyrosine / metabolism
Protein Kinase C / physiology*
Protein Processing, Post-Translational
Proto-Oncogene Proteins / physiology*
Tetradecanoylphorbol Acetate / pharmacology*
Time Factors
src-Family Kinases / physiology*
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Bryostatins; 0/Carcinogens; 0/Lactones; 0/Macrolides; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 1114-81-4/Phosphothreonine; 16561-29-8/Tetradecanoylphorbol Acetate; 17885-08-4/Phosphoserine; 21820-51-9/Phosphotyrosine; 83314-01-6/bryostatin 1; EC Specific Protein Tyrosine Kinase p56(lck); EC Kinases; EC Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Ligation of CD53/OX44, a tetraspan antigen, induces homotypic adhesion mediated by specific cell-cel...
Next Document:  Potentiation of antitumor CTL response by GM-CSF involves a B7-dependent mechanism.