The SH3 domain of Bruton's tyrosine kinase displays altered ligand binding properties when auto-phosphorylated in vitro.

Abstract:

:Btk is a member of the Tec family of protein tyrosine kinases expressed in B cells. It is stimulated following cross-linking of the B cell receptor which leads to the autophosphorylation of a specific residue in the SH3 domain, Y223. Previous work using Btk-derived fusion proteins has shown that the Btk SH3 domain binds to c-Cbl and Wiskott-Aldrich syndrome protein (WASP) in vitro. We show here that when the Btk SH3 domain fusion protein is autophosphorylated, its ability to take part in protein interactions is altered as compared to the non-phosphorylated fusion protein. Although the phosphorylated Btk SH3 domain still binds c-Cbl, it no longer binds WASP and instead acquires a high affinity for kinase-active Syk. The region of Syk responsible for this interaction is contained within its C terminus, suggesting a novel mechanism by which these proteins may interact.

journal_name

Eur J Immunol

authors

Morrogh LM,Hinshelwood S,Costello P,Cory GO,Kinnon C

doi

10.1002/(SICI)1521-4141(199907)29:07<2269::AID-IMM

keywords:

subject

Has Abstract

pub_date

1999-07-01 00:00:00

pages

2269-79

issue

7

eissn

0014-2980

issn

1521-4141

journal_volume

29

pub_type

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