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

Y W Su; Y Zhang; J Schweikert; G A Koretzky; M Reth; J Wienands

doi:10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R

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

Eur J Immunol. 1999 Nov;29(11):3702-11. doi: 10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R.

Authors

Y W Su¹, Y Zhang, J Schweikert, G A Koretzky, M Reth, J Wienands

Affiliation

¹ Abteilung für Molekulare Immunologie Biologie III, Universität Freiburg und Max-Planck-Institut für Immunbiologie, Freiburg, Germany.

Abstract

Activation of lymphocytes through their antigen receptors leads to mobilization of intracellular Ca(2+) ions. This process requires expression of SLP adaptors and involves phosphorylation of phospholipase C-gamma 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-gamma 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-gamma both bind via their SH2 domain to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C-gamma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Agammaglobulinaemia Tyrosine Kinase
B-Lymphocytes / metabolism*
Carrier Proteins*
Cell Line
Glutathione Transferase / metabolism
Humans
Jurkat Cells
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*
Tyrosine / metabolism
src Homology Domains*

Substances

Adaptor Proteins, Signal Transducing
B cell linker protein
Carrier Proteins
Phosphoproteins
Receptors, Antigen, B-Cell
Receptors, Immunologic
Recombinant Fusion Proteins
SLP-76 signal Transducing adaptor proteins
Tyrosine
Glutathione Transferase
LTK protein, human
Protein-Tyrosine Kinases
Receptor Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase
BTK protein, human