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.
Umemori
H
H
Department of Oncology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Hayashi
T
T
Inoue
T
T
Nakanishi
S
S
Mikoshiba
K
K
Yamamoto
T
T
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction
D017027:Protein Tyrosine Phosphatases; D019204:GTP-Binding Proteins