The Wiskott-Aldrich syndrome (WAS) is characterized by thrombocytopenia,
eczema, defects in cell-mediated and humoral immunity and a propensity for
lymphoproliferative diseases. The syndrome is the result of a mutation in
the gene encoding a proline-rich protein termed WASP. WASP has been
identified as a downstream effector of Cdc42 and has been implicated in Actin
polymerization and cytoskeletal organization. A distantly related protein, VASP
(vasodilator-stimulated phosphoprotein), is involved in the maintenance of
cytoarchitecture by interacting with Actin-like filaments. VASP shares a limited
degree of homology with the amino terminus of WASP, which is frequently
mutated in WAS patients. An established substrate of cAMP and cGMP
dependent kinases, VASP is phosphorylated on a regulatory serine residue
157 and localizes to focal adhesions, microfilaments and highly active regions
of the plasma membrane. VASP is highly expressed in human platelets and,
like WASP, may play a role in cytoskeletal organization.