Recent advances in the biology of WASP and WIP.
WASP, the product of the gene mutated in Wiskott-Aldrich syndrome, is expressed only in hematopoietic cells and is the archetype of a family of proteins that include N-WASP and Scar/WAVE. WASP plays a critical role in T cell activation and actin reorganization. WASP has multiple protein-interacting domains. Through its N-terminal EVH1 domain WASP binds to its partner WASP interacting protein (WIP) and through its C-terminal end it interacts with and activates the Arp2/3 complex. In lymphocytes, most of WASP is sequestered with WIP and binding to WIP is essential for the stability of WASP. The central proline-rich region of WASP serves as docking site to several adaptor proteins. Through these multiple interactions WASP integrates many cellular signals to actin cytoskeleton remodeling. In this review, we have summarized recent developments in the biology of WASP and the role of WIP in regulating WASP function. We also discuss WASP-independent functions of WIP.
Ramesh
Narayanaswamy
N
Division of Immunology, Department of Pediatrics, Childrens Hospital, Harvard Medical School, Karp 10 One Blackfan Circle, Boston, MA, 02115, USA.
Geha
Raif
R
D051376:Actin-Related Protein 2-3 Complex / Q000276:immunology / Q000378:metabolism; D000199:Actins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D017434:Protein Structure, Tertiary / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology* / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000276:immunology / Q000378:metabolism
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C109903:WIPF1 protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein