The Wiskott-Aldrich syndrome protein: forging the link between actin and cell activation.
The Wiskott-Aldrich syndrome protein (WASp) has emerged as a central player in the regulation of actin remodeling in T cells. The unique domain structure of WASp and other WASp family members enables these proteins to associate with a myriad of signaling effectors and to thereby regulate the coupling of T cell antigen receptor (TCR) engagement to both cytoskeletal rearrangement and transcriptional activation. This review focuses on these biochemical properties of WASp and also on the mechanisms whereby WASp interactions with its cognate ligands influence T cell activation. Because of its capacity to shift intracellular location and thereby dictate both the timing and the spatial distribution of actin polymerization following cell stimulation, WASp is well positioned to play major regulatory roles in directing a wide range of cellular processes and signaling pathways. Further dissection of the functional and biochemical properties of WASp therefore represents a promising avenue towards defining the molecular mechanisms that convey TCR stimulatory signals to the actin cytoskeleton and integrate cytoskeletal and other signaling systems so as to evoke a biological response.
Badour
Karen
K
Department of Medicine, Immunology and Medical Genetics and Microbiology, University of Toronto, Samuel Ontario, Canada.
Zhang
Jinyi
J
Siminovitch
Katherine A
KA
D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003598:Cytoskeletal Proteins; D006801:Humans; D008213:Lymphocyte Activation; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein