Protein-tyrosine Phosphatase-α and Src Functionally Link Focal Adhesions to the Endoplasmic Reticulum to Mediate Interleukin-1-induced Ca2+ Signaling

Calcium (Ca 2+ ) signaling by the pro-inflammatory cytokine interleukin-1 (IL-1) is dependent on focal adhesions, which contain diverse structural and signaling proteins including protein phosphatases. We examined here the role of protein-tyrosine phosphatase (PTP) α in regulating IL-1-induced Ca 2+ signaling in fibroblasts. IL-1 promoted recruitment of PTPα to focal adhesions and endoplasmic reticulum (ER) fractions, as well as tyrosine phosphorylation of the ER Ca 2+ release channel IP 3 R. In response to IL-1, catalytically active PTPα was required for Ca 2+ release from the ER, Src-dependent phosphorylation of IP 3 R1 and accumulation of IP 3 R1 in focal adhesions. In pulldown assays and immunoprecipitations PTPα was required for the association of PTPα with IP 3 R1 and c-Src, and this association was increased by IL-1. Collectively, these data indicate that PTPα acts as an adaptor to mediate functional links between focal adhesions and the ER that enable IL-1-induced Ca 2+ signaling.