title: Tyrosine phosphorylation of WASP promotes calpain-mediated podosome disassembly.
abstract: Podosomes are actin-based adhesions involved in migration of cells that have to cross tissue boundaries such as myeloid cells. The Wiskott Aldrich Syndrome Protein regulates de novo actin polymerization during podosome formation and it is cleaved by the protease calpain during podosome disassembly. The mechanisms that may induce the Wiskott Aldrich Syndrome Protein cleavage by calpain remain undetermined. We now report that in myeloid cells, tyrosine phosphorylation of the Wiskott Aldrich Syndrome Protein-tyrosine291 (Human)/tyrosine293 (mouse) not only enhances Wiskott Aldrich Syndrome Protein-mediated actin polymerization but also promotes its calpain-dependent degradation during podosome disassembly. We also show that activation of the Wiskott Aldrich Syndrome Protein leading to podosome formation occurs independently of tyrosine phosphorylation in spleen-derived dendritic cells. We conclude that tyrosine phosphorylation of the Wiskott Aldrich Syndrome Protein integrates dynamics of actin and cell adhesion proteins during podosome disassembly required for mobilization of myeloid cells during the immune response.
authors: Department of Haemato-oncology, King's College London, London, UK.
authors: Lee
authors: L
authors: Macpherson
authors: James
authors: J
authors: Monypenny
authors: Michael P
authors: MP
authors: Blundell
authors: Giles O
authors: GO
authors: Cory
authors: Jessica
authors: J
authors: Tomé-García
authors: Adrian J
authors: AJ
authors: Thrasher
authors: Gareth E
authors: GE
authors: Jones
authors: Yolanda
authors: Y
authors: Calle
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D002448:Cell Adhesion; D021961:Cell Membrane Structures / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D014443:Tyrosine / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein / Q000502:physiology*
chemical_list: C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D014443:Tyrosine; D002154:Calpain