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- W2068374462 abstract "The dimeric Gh protein is comprised of α (tissue transglutaminase) and β (Calreticulin) subunits and known to be associated with FSH-, oxytocin-, or epinephrine-receptors/functions in their respective target cells. After establishing the FSH-induced activation of Gαh/phospholipase C (PLC)-δ1 pathway in rat Sertoli cells (SCs), we have attempted to identify a possible Gαh-coupled novel FSH receptor (FSH-R). Remarkably, a protein with approximately 240-kDa molecular mass was coimmunoprecipitated with Gαh in the fractionated membrane proteins of rat SCs. The protein was identified as myosin heavy polypeptide 9 (MyH9) by mass spectrometric analysis and immunoblotting. In addition, immunoprecipitation analysis reveals that MyH9 is constitutively associated with classical Gs-coupled FSH-R and inactive GDP-bound Gαh at resting state of rat SCs, but did not interact with FSH directly as judged by Far-Western analysis. Upon the stimulation of higher levels of extracellular FSH (>1000 IU/liter), classical FSH-R induces the phosphorylation of MyH9, the dissociation of active GTP-bound Gαh from FSH-R:MyH9 complexes, and the elicitation of Gαh/PLC-δ1 pathway-dependent Ca2+-influx in rat SCs. Furthermore, the specific inhibition of MyH9 ATPase activity with Blebbistatin dose-dependently suppressed FSH-induced Gαh/PLC-δ1 signaling and Ca2+-influx, but not intracellular cAMP accumulation in rat SCs, implying that MyH9 mediates FSH-induced activation of Gαh/PLC-δ1/IP3/Ca2+-influx pathway in rat SCs. This is the first to demonstrate that the filament protein MyH9 constitutively forms a ternary complex with FSH-R and inactive GDP-bound Gαh. At higher FSH levels, this ternary complex executes an alternative signaling of classical Gs-coupled FSH-R through activating a Gs/cAMP-independent, Gαh/PLC-δ1 pathway in rat SCs." @default.
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- W2068374462 date "2010-01-12" @default.
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- W2068374462 title "Nonmuscle Myosin IIA (Myosin Heavy Polypeptide 9): A Novel Class of Signal Transducer Mediating the Activation of Gαh/Phospholipase C-δ1 Pathway" @default.
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- W2068374462 doi "https://doi.org/10.1210/en.2009-0722" @default.
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