Interactions of the protein-tyrosine phosphatase-{alpha} with the FAT domain of focal adhesion kinase are involved in IL-1 signaling in fibroblasts [Cell Biology]

May 12th, 2014 by Wang, Q., Wang, Y., Fritz, D., Rajshankar, D., Downey, G. P., McCulloch, C. A.

Interleukin-1 (IL-1) signaling in fibroblasts is mediated through focal adhesions, organelles that are enriched with adaptor and cytoskeletal proteins that regulate signal transduction. We examined interactions of the focal adhesion kinase (FAK) with protein tyrosine phosphatase-alpha (PTP-alpha) in IL-1 signaling. In wild type and FAK knockout mouse embryonic fibroblasts, we found by immunoblotting, immunoprecipitation and immunostaining that FAK is required for IL-1-mediated sequestration of PTPalpha to focal adhesions. Immunoprecipitation and pull-down assays of purified proteins demonstrated a direct interaction between FAK and PTPalpha, which was dependent on the FAT domain of FAK and by an intact membrane-proximal phosphatase domain of PTPalpha. Recruitment of PTPalpha to focal adhesions, IL-1-induced Ca2+ release from the endoplasmic reticulum, ERK activation, and IL-6, MMP-3 and MMP-9 expression were all blocked in FAK knockout fibroblasts. These processes were restored in FAK knockout cells transfected with wild type FAK, FAT domain and FRNK. Our data indicate that IL-1-induced signaling through focal adhesions involves interactions between the FAT domain of FAK and PTPalpha.
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