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Tyrosine phosphorylation of WIP releases bound WASP and impairs podosome assembly in macrophages.
- Source :
-
Journal of Cell Science . 1/15/2015, Vol. 128 Issue 2, p251-265. 15p. 1 Chart. - Publication Year :
- 2015
-
Abstract
- Podosomes are integrin-containing adhesion structures commonly found in migrating leukocytes of the monocytic lineage. The actin cytoskeletal organisation of podosomes is based on a WASP- and Arp2/3-mediated mechanism. WASP also associates with a second protein, WIP (also known as WIPF1), and they co-localise in podosome cores. Here, we report for the first time that WIP can be phosphorylated on tyrosine residues and that tyrosine phosphorylation of WIP is a trigger for release of WASP from the WIP-WASP complex. Using a knockdown approach together with expression of WIP phosphomimics, we show that in the absence of WIP-WASP binding, cellular WASP is rapidly degraded, leading to disruption of podosomes and a failure of cells to degrade an underlying matrix. In the absence of tyrosine phosphorylation, the WIP-WASP complex remains intact and podosome lifetimes are extended. A screen of candidate kinases and inhibitor-based assays identified Bruton's tyrosine kinase (Btk) as a regulator of WIP tyrosine phosphorylation. We conclude that tyrosine phosphorylation of WIP is a crucial regulator of WASP stability and function as an actin-nucleation-promoting factor. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TYROSINE
*PHOSPHORYLATION
*CYTOSKELETON
*MACROPHAGES
*MONOCYTES
Subjects
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 128
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 103375709
- Full Text :
- https://doi.org/10.1242/jcs.154880