TY - JOUR
T1 - Involvement of protein tyrosine phosphatases in activation of the trimeric G protein G(q/11)
AU - Umemori, Hisashi
AU - Hayashi, Takashi
AU - Inoue, Takafumi
AU - Nakanishi, Shigetada
AU - Mikoshiba, Katsuhiko
AU - Yamamoto, Tadashi
N1 - Funding Information:
We thank N Sekiyama for assistance with measuring IP3 formation, Y Bessho for assistance with Ca2+ imaging, K Haga, T Haga, K Kimura and H Itoh for valuable discussion. This work is supported by a grant for Advanced Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan.
PY - 1999/12/2
Y1 - 1999/12/2
N2 - 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).
AB - 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).
KW - G protein
KW - Gα(q/11)
KW - IP3
KW - Metabotropic glutamate receptor
KW - Tyrosine phosphatase
KW - Tyrosine phosphorylation
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U2 - 10.1038/sj.onc.1203152
DO - 10.1038/sj.onc.1203152
M3 - Article
C2 - 10602498
AN - SCOPUS:0033518142
SN - 0950-9232
VL - 18
SP - 7399
EP - 7402
JO - Oncogene
JF - Oncogene
IS - 51
ER -
