Interaction of SLP adaptors with the SH2 domain of Tec family kinases

Activation of lymphocytes through their antigen receptors leads to mobilization of intracellular Ca2+ ions. This process requires expression of SLP adaptors and involves phosphorylation of phospholipase C‐γ isoforms by the Tec‐related protein tyrosine kinase Btk in B cells and Itk in T cells. The SH...

Full description

Saved in:
Bibliographic Details
Published in:European journal of immunology 1999-11, Vol.29 (11), p.3702-3711
Main Authors: Su, Yu‐Wen, Zhang, Yong, Schweikert, Jutta, Koretzky, Gary A., Reth, Michael, Wienands, Jürgen
Format: Article
Language:English
Subjects:
Adaptor protein
adaptor proteins
Adaptor Proteins, Signal Transducing
agammaglobulinemia
B-Lymphocytes - metabolism
Btk protein
Carrier Proteins
Cell Line
Glutathione Transferase - metabolism
Humans
Itk protein
Jurkat Cells
Lymphocyte antigen receptor
Phosphoproteins - isolation & purification
Phosphoproteins - metabolism
Phosphorylation
Protein-Tyrosine Kinases - isolation & purification
Protein-Tyrosine Kinases - metabolism
Receptor Protein-Tyrosine Kinases - metabolism
Receptors, Antigen, B-Cell - metabolism
Receptors, Immunologic
Recombinant Fusion Proteins - metabolism
Signal Transduction
SLP protein
Src homology 2 domain
src Homology Domains
Tyrosine - metabolism
Tyrosine phosphorylation
XLA
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Activation of lymphocytes through their antigen receptors leads to mobilization of intracellular Ca2+ ions. This process requires expression of SLP adaptors and involves phosphorylation of phospholipase C‐γ isoforms by the Tec‐related protein tyrosine kinase Btk in B cells and Itk in T cells. The SH2 domain of Btk and Itk is essential for phospholipase C‐γ phosphorylation and mutations in this domain lead to the X‐linked agammaglobulinemia immuno deficiency in humans. Here we show that, in contrast to SH2 domains from other signaling proteins, the Btk and Itk SH2 domains exhibit a restricted binding specificity. They bind selectively to tyrosine‐phosphorylated SLP‐65 and SLP‐76 in activated B and T cells, respectively. Our findings suggest that Btk / Itk and phospholipase C‐γ both bind via their SH2 domain to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C‐γ.
ISSN:0014-2980
1521-4141
DOI:10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R