Involvement of protein tyrosine phosphatases in activation of the trimeric G protein G(q/11)

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