Posted by: Dan | March 12, 2007

Paxillin Phosphorylation and Cell Adhesion

An interesting report, covered in the Cell Migration Gateway’s March update (emphasis mine):

The focal adhesion-associated adaptor protein paxillin is phosphorylated upon integrin activation or growth factor stimulation. Many paxillin phosphorylation sites have been mapped but in most cases, their effect on the protein’s function has not been characterised. In a study published in the Journal of Cell Science, Geiger and colleagues have investigated the role of paxillin tyrosine phosphorylation at residues 31 and 118 on endothelial cell adhesion. Using phosphospecific antibodies, they show that tyrosine phosphorylated paxillin localizes to focal complexes and focal adhesions but not to fibrillar adhesions. Expression of a phosphomimetic paxillin mutant not only increased adhesion assembly and turnover, but also stimulated the formation of lamellipodial protrusions. Conversely, a non-phosphorylatable paxillin mutant was found to stabilise adhesion sites. The authors also show that paxillin phosphorylation is negatively regulated by mechanical force and that focal adhesion kinase (FAK) is a key mediator of the phosphopaxillin-induced disassembly of adhesions. Together, this data has enabled the creation of a mathematical model which suggests that tyrosine phosphorylation of paxillin acts as a crucial switch in the regulation adhesion dynamics.

It’s been a while since I brought up paxillin, which is a scaffolding protein which modulates network interactions amongst a variety of proteins related to cell adhesion. By “modulates network interactions” though, I really mean that paxillin (and many other gene products) doesn’t really have a clear-cut function, as the Behe-mousetrap creationists would argue. Its interactions are fickle, subtle and complex, and – more importantly perhaps – very plastic.

In this instance, the phosphorylation of a particular amino acid modulates the activity, interactions, and location of paxillin.

Paxillin phosphorylation

Reference:

  • Zaidel-Bar R, Milo R, Kam Z, Geiger B. A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions. J Cell Sci 2007; 120 (Pt 1):137-48 PubMed

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