Galphaq/11 signaling induces apoptosis through two pathways involving reduction of Akt phosphorylation and activation of RhoA in HeLa cells

Experimental Cell Research
Hiroshi UedaTomiko Asano

Abstract

We have previously reported that expression of the constitutively active mutant of Galpha11 or stimulation of m1 muscarinic acetylcholine receptor induced proteolytic activation of Rho-associated kinase (ROCK-I) by caspase and apoptosis in HeLa cells. In this study, we investigate the molecular mechanisms of Galphaq/11-induced apoptosis in m1 muscarinic acetylcholine receptor-expressing HeLa cells. Overexpression of Bcl-2 inhibited carbachol-induced ROCK-I cleavage, indicating a mitochondrial apoptotic pathway. Overexpression of the constitutively active mutant of Akt that delivers an anti-apoptotic survival signal had a similar influence. Insulin, a major survival factor in many cells, strongly increased phosphorylation of Akt, which was completely blocked by carbachol. This latter effect was partially inhibited by treatment with the tyrosine phosphatase inhibitors, orthovanadate and pervanadate. In parallel with these observations, carbachol attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1, an effect eliminated by orthovanadate. On the other hand, carbachol induced rapid stimulation of endogenous RhoA, and expression of a constitutively active mutant of RhoA increased ROCK-I cleavage. Ort...Continue Reading

References

May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·P F JonesB A Hemmings
Mar 15, 1997·Experimental Cell Research·E CigolaP Anversa
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·D E Clapham, E J Neer
Sep 26, 1997·The Journal of Biological Chemistry·H AlthoeferM I Simon
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·S P HeximerJ R Hepler
Aug 26, 1998·Proceedings of the National Academy of Sciences of the United States of America·J W AdamsG W Dorn
Apr 25, 2000·Molecular and Cellular Biology·R L BoshansC D'Souza-Schorey
Jun 6, 2000·The Journal of Biological Chemistry·K KimuraS Narumiya
Sep 15, 2000·The Journal of Biological Chemistry·R K BommakantiW F Simonds
Oct 26, 2000·Nature·M O Hengartner
May 23, 2002·The Journal of Biological Chemistry·Hiroki ChikumiJ Silvio Gutkind
May 25, 2002·Molecular and Cellular Biology·Michelle A BoodenChanning J Der
Oct 24, 2002·The Journal of Biological Chemistry·Christian E WredeChristopher J Rhodes
Jul 1, 1993·Trends in Cell Biology·J Iñiguez-LluhiA G Gilman

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Citations

Mar 10, 2007·Archivum Immunologiae Et Therapiae Experimentalis·Jianjian Shi, Lei Wei
Aug 29, 2009·Cell Communication and Signaling : CCS·Rodrigo R Resende, Avishek Adhikari
Oct 2, 2007·European Journal of Haematology·Masayuki KoizumiYasushi Saito
Dec 19, 2018·Molecular and Cellular Biology·Arshiya BanuAgamemnon E Grigoriadis
Aug 7, 2009·American Journal of Physiology. Cell Physiology·Abduqodir H ToychievYasunobu Okada
Jul 5, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Salma TaboubiMaxime Lehmann
Aug 27, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christina M WuertzSusanne Lutz
Jun 15, 2007·The Journal of Biological Chemistry·Vijay YanamadalaBradley M Denker
Sep 27, 2005·Cellular Signalling·Katherine B Hubbard, John R Hepler

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