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PMID: 10852954 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of protein kinase CbetaI by two protein-tyrosine kinases, Btk and Syk.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 13 ·2000-06-20 ·Pages 7423-8

Kawakami Y, Kitaura J, Hartman SE, Lowell CA, Siraganian RP, Kawakami T

Abstract

Two protein-tyrosine kinases, Bruton's tyrosine kinase (Btk) and Syk, and members of the protein kinase C (PKC) subfamily of serine/threonine kinases play crucial roles in signal transduction through antigen receptors in B lymphocytes and high-affinity IgE receptors (FcepsilonRI) in mast cells. The present study provides genetic, biochemical, and pharmacological evidence that, on FcepsilonRI stimulation, Syk regulates Btk, and Btk selectively regulates the membrane translocation and enzymatic activity of PKCbetaI among the conventional PKC isoforms (alpha, betaI, and betaII) expressed in mast cells. Syk/Btk-mediated PKCbetaI regulation is involved in transcriptional activation of the IL-2 and tumor necrosis factor alpha genes through the JNK pathway induced by FcepsilonRI stimulation. Accordingly, FcepsilonRI-induced production of these cytokines is inhibited by specific inhibitors of Btk and Syk, as well as broad-specificity inhibitors of PKC and a selective inhibitor of PKCbeta. Specific regulation of PKCbetaI by Btk is consistent with the selective association of Btk with PKCbetaI. Components of this signaling pathway may represent an attractive set of potential targets of pharmaceutical interference for the treatment of allergic and other immunologic diseases.

MeSH Terms
Agammaglobulinaemia Tyrosine Kinase Animals B-Lymphocytes/immunology Cells, Cultured Enzyme Precursors/immunology Intracellular Signaling Peptides and Proteins Isoenzymes/immunology Mice Mice, Knockout Protein Kinase C/immunology Protein Kinase C beta Protein-Tyrosine Kinases/immunology Signal Transduction/immunology Syk Kinase
Chemicals
Enzyme Precursors Intracellular Signaling Peptides and Proteins Isoenzymes Protein-Tyrosine Kinases Agammaglobulinaemia Tyrosine Kinase Btk protein, mouse Syk Kinase Syk protein, mouse Protein Kinase C Protein Kinase C beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kawakami Y
Division of Allergy, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
Kitaura J
Hartman S E
Lowell C A
Siraganian R P
Kawakami T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.120175097
Published
2000-06-20
Pages
7423-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC16561
Subset
IM
Grants
NIAID NIH HHS · R01 AI038348 · United States
NIAID NIH HHS · AI33617 · United States
NIAID NIH HHS · AI38348 · United States
NIAID NIH HHS · U19 AI42244 · United States
External Links
PubMed source DOI: 10.1073/pnas.120175097 PMC Full Text View journal details
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