THE SH3 DOMAIN OF BRUTONS TYROSINE KINASE INTERACTS WITH VAV, SAM68 AND EWS

Bruton tyrosine kinase (BTK) is a cytoplasmic protein tyrosine kinase which controls crucial steps of differentiation of B lymphocytes. Muta tions affecting either the PH, SH3, SH2 or kinase domain of BTK all gi ve rise to X linked agammaglobulinaemia (XLA) in humans. In this study , the authors report that the BTK-SH3 domain binds to a set of protein s expressed in pro-B, pre-B and B cell lines. Three of them were chara cterized as Vav, Sam68 and EWS. The authors show that a Pro --> Leu su bstitution in a region of the SH3 domain, which is deleted in an XLA p atient, is sufficient to abolish BTK-SH3 binding potential. The author s also report that several of the BTK-SH3 binding proteins, including Sam68, EWS and Vav, are tyrosine phosphorylated in conditions that als o promote BTK kinase activity. For EWS and Sam68 this tyrosine phospho rylation was cell cycle dependent.