Document Detail


Protein kinase C plays a role in the induction of tyrosine phosphorylation of lymphoid microtubule-associated protein-2 kinase. Evidence for a CD3-associated cascade that includes pp56lck and that is defective in HPB-ALL.
MedLine Citation:
PMID:  1716287     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ligation of the CD3 receptor induces multiple signal transduction events that modify the activation state of the T cell. We have compared two lines that express biologically active CD3 receptors but differ in their biochemical activation pathways during ligation of this receptor. Jurkat cells respond to anti-CD3 with Ca2+ mobilization, PKC activation, induction of protein tyrosine phosphorylation, and activation of newly characterized lymphoid microtubule associated protein-2 kinase (MAP-2K). MAP-2K itself is a 43-kDa phosphoprotein that requires tyrosine phosphorylation for activation. Although ligation of the CD3 receptor in HPB-ALL could stimulate tyrosine phosphorylation of a 59- kDa substrate, there was no associated induction of [Ca2+]i flux, PKC, or MAP-2K activation. A specific PKC agonist, PMA, which bypasses the CD3 receptor, could, however, activate MAP-2K in HPB-ALL cells. This implies that defective stimulation of PKC by the CD3 receptor is responsible for its failure to activate MAP-2K in HPB-ALL. The defect in PKC activation is likely distal to the CD3 receptor as A1F14- failed to activate MAP-2K in HPB-ALL but was effective in Jurkat cells. The stimulatory effect of PMA on MAP-2K activity in HPB-ALL was accompanied by tyrosine phosphorylation of this kinase which implies that PKC may, in some way, regulate tyrosine phosphorylation of MAP-2K. A candidate for this role is pp56lck which underwent posttranslational modification (seen as mobility change on SDS-PAGE) during anti-CD3 and PMA stimulation in Jurkat or PMA treatment in HPB-ALL. There was, in fact, exact coincidence between induction of PKC activity, posttranslational modification of lck and tyrosine phosphorylation/activation of MAP-2K. Lck kinase activity in an immune complex kinase assay was unchanged during PMA treatment. An alternative explanation is that modification of lck may alter its substrate profile. We therefore looked at the previously documented ability of PKC to dissociate lck from the CD4 receptor and found that PMA could reduce the stoichiometry of the lck interaction with CD4 in HPB-ALL and to a lesser extent in Jurkat cells. These results imply the existence of a kinase cascade that is initiated by PKC and, in the course of which, lck and MAP-2K may interact.
Authors:
A E Nel; C Hanekom; L Hultin
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  147     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-10-17     Completed Date:  1991-10-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1933-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, UCLA School of Medicine 90024.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD3
Antigens, Differentiation, T-Lymphocyte / physiology*
Calcium-Calmodulin-Dependent Protein Kinases
Enzyme Activation
Humans
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Lymphocytes / metabolism*
Molecular Weight
Phosphoproteins / chemistry,  metabolism
Phosphorylation
Phosphotyrosine
Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Protein Kinase C / physiology*
Protein Kinases / metabolism*
Protein-Tyrosine Kinases / metabolism*
Proto-Oncogene Proteins / metabolism*
Receptors, Antigen, T-Cell / physiology*
Signal Transduction
Tetradecanoylphorbol Acetate / pharmacology
Tumor Cells, Cultured
Tyrosine / analogs & derivatives,  metabolism
Grant Support
ID/Acronym/Agency:
AI 15332/AI/NIAID NIH HHS; GM 41576/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD3; 0/Antigens, Differentiation, T-Lymphocyte; 0/Phosphoproteins; 0/Proto-Oncogene Proteins; 0/Receptors, Antigen, T-Cell; 16561-29-8/Tetradecanoylphorbol Acetate; 21820-51-9/Phosphotyrosine; 55520-40-6/Tyrosine; EC 2.7.-/Protein Kinases; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/Lymphocyte Specific Protein Tyrosine Kinase p56(lck); EC 2.7.11.13/Protein Kinase C; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases

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


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