Involvement of protein tyrosine phosphatases in activation of the trimeric G protein Gq/11.

A variety of receptors coupled to the heterotrimeric guanine nucleotide-binding protein Gq/11 stimulate intracellular Ca2+ release through inositol (1,4,5)-trisphosphate (IP3) formation. We previously reported that tyrosine phosphorylation of the alpha subunit of the Gq/11 protein by protein tyrosine kinases (PTKs) regulates the activation of Gq/11 protein. Here we show that protein tyrosine phosphatases (PTPs) are also essential for Gq/11 protein activation. We find that Gq/11 protein-coupled receptor-mediated formation of IP3 is blocked by PTP inhibitors as well as PTK inhibitors. These inhibitors act prior to Gq/11 protein activation. Tyrosine phosphorylation of the alpha subunit of Gq/11 appears to inhibit its interaction with receptors. Thus, PTP is required for controlling the level of tyrosine phosphorylation of the alpha subunit of Gq/11 to promote its interaction with receptors. Therefore, we conclude that PTKs and PTPs co-operate to proceed activation cycle of the Gq/11 protein through tyrosine phosphorylation and de-phosphorylation of the alpha subunit of Gq/11.