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PMID: 7500027 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling.

The Journal of experimental medicine ·Vol. 182 ·No. 6 ·1995-12-01 ·Pages 1815-23

Kurosaki T, Johnson SA, Pao L, Sada K, Yamamura H, Cambier JC

Abstract

To explore the mechanism(s) by which the Syk protein tyrosine kinase participates in B cell antigen receptor (BCR) signaling, we have studied the function of various Syk mutants in B cells made Syk deficient by homologous recombination knockout. Both Syk SH2 domains were required for BCR-mediated Syk and phospholipase C (PLC)-gamma 2 phosphorylation, inositol 1,4,5-triphosphate release, and Ca2+ mobilization. A possible explanation for this requirement was provided by findings that recruitment of Syk to tyrosine-phosphorylated immunoglobulin (Ig) alpha and Ig beta requires both Syk SH2 domains. A Syk mutant in which the putative autophosphorylation site (Y518/Y519) of Syk was changed to phenylalanine was also defective in signal transduction; however, this mutation did not affect recruitment to the phosphorylated immunoreceptor family tyrosine-based activation motifs (ITAMs). These findings not only confirm that both SH2 domains are necessary for Syk binding to tyrosine-phosphorylated Ig alpha and Ig beta but indicate that this binding is necessary for Syk (Y518/519) phosphorylation after BCR ligation. This sequence of events is apparently required for coupling the BCR to most cellular protein tyrosine phosphorylation, to the phosphorylation and activation of PLC-gamma 2, and to Ca2+ mobilization.

MeSH Terms
Amino Acid Sequence B-Lymphocytes/immunology Calcium/metabolism Cells, Cultured Enzyme Precursors/metabolism Inositol 1,4,5-Trisphosphate/metabolism Intracellular Signaling Peptides and Proteins Molecular Sequence Data Mutagenesis, Site-Directed Peptides/chemistry Phosphorylation Protein-Tyrosine Kinases/metabolism Receptors, Antigen, B-Cell/metabolism Signal Transduction Structure-Activity Relationship Syk Kinase src Homology Domains
Chemicals
Enzyme Precursors Intracellular Signaling Peptides and Proteins Peptides Receptors, Antigen, B-Cell Inositol 1,4,5-Trisphosphate Protein-Tyrosine Kinases Syk Kinase Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kurosaki T
Department of Cardiovascular Molecular Biology, Lederle Laboratories, Pearl River, New York 10965, USA.
Johnson S A
Pao L
Sada K
Yamamura H
Cambier J C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.182.6.1815
Published
1995-12-01
Pages
1815-23
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192262
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.182.6.1815 PMC Full Text View journal details
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