Tyrosine phosphorylation of the Wiskott‐Aldrich Syndrome protein by Lyn and Btk is regulated by CDC42

FEBS Letters

Chavrier, Philippe¹  Fougereau, Michel¹  Guinamard, Rodolphe¹  Aspenström, Pontus²  Guillemot, Jean-Claude¹ 

[1] Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France;Ludwig Institute for Cancer Research, Biomedical Center, Box 595, 751 24 Uppsala, Sweden

关键词: Tyrosine phosphorylation;    Wiskott-Aldrich syndrome gene product;    CDC42;    FcϵRI;   

DOI  :  10.1016/S0014-5793(98)01016-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The Wiskott-Aldrich syndrome (WAS) is a rare immunodeficiency disease affecting mainly platelets and lymphocytes. Here, we show that the WAS gene product, WASp, is tyrosine phosphorylated upon aggregation of the high affinity IgE receptor (FcϵRI) at the surface of RBL-2H3 rat tumor mast cells. Lyn and the Bruton's tyrosine kinase (Btk), two protein tyrosine kinases involved in FcϵRI-signaling phosphorylate WASp and interact with WASp in vivo. Interestingly, expression of a GTPase defective mutant form of CDC42, that interacts with WASp, is accompanied by a substantial increase in WASp tyrosine phosphorylation. This study suggests that activated CDC42 recruits WASp to the plasma membrane where it becomes phosphorylated by Lyn and Btk. We conclude that WASp represents a connection between protein tyrosine kinase signaling pathways and CDC42 function in cytoskeleton and cell growth regulation in hematopoietic cells.

【 授权许可】

Unknown