Gα13-mediated transformation and apoptosis are permissively dependent on basal ERK activity

Vyacheslav A. Adarichev, Rita Vaiskunaite, Jiaxin Niu, Irina V. Balyasnikova, Tatyana A. Voyno-Yasenetskaya

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We previously reported that the α-subunit of heterotrimeric G 13 protein induces either mitogenesis and neoplastic transformation or apoptosis in a cell-dependent manner. Here, we analyzed which signaling pathways are required for Gα13-induced mitogenesis or apoptosis using a novel mutant of Gα13. We have identified that in human cell line LoVo, the mutation encoding substitution of Arg260 to stop codon in mRNA of Gα13 subunit produced a mutant protein (Gα13-T) that lacks a COOH terminus and is endogenously expressed in LoVo cells as a polypeptide of 30 kDa. We found that Gα 13-T lost its ability to promote proliferation and transformation but retained its ability to induce apoptosis. We found that full-length Gα13 could stimulate Elk1 transcription factor, whereas truncated Gα13 lost this ability. Gα 13-dependent stimulation of Elk1 was inhibited by dominant-negative extracellular signal-regulated kinase (MEK) but not by dominant-negative MEKK1. Similarly, MEK inhibitor PD-98059 blocked Gα13-induced Elk1 stimulation, whereas JNK inhibitor SB-203580 was ineffective. In Rat-1 fibroblasts, Gα13-induced cell proliferation and foci formation were also inhibited by dominant-negative MEK and PD-98059 but not by dominant-negative MEKK1 and SB-203580. Whereas Gα13-T alone did not induce transformation, coexpression with constitutively active MEK partially restored its ability to transform Rat-1 cells. Importantly, full-length but not Gα13-T could stimulate Src kinase activity. Moreover, Gα13-dependent stimulation of Elk1, cell proliferation, and foci formation were inhibited by tyrosine kinase inhibitor, genistein, or by dominant-negative Src kinase, suggesting the involvement of a Src-dependent pathway in the Gα13-mediated cell proliferation and transformation. Importantly, truncated Gα13 retained its ability to stimulate apoptosis signal-regulated kinase ASK1 and c-Jun terminal kinase, JNK. Interestingly, the apoptosis induced by Gα13-T was inhibited by dominant-negative ASK1 or by SB-203580.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number4 54-4
Publication statusPublished - Oct 1 2003
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinase Kinases
Apoptosis
Cell proliferation
src-Family Kinases
Cell Proliferation
G12-G13 GTP-Binding Protein alpha Subunits
Rats
ets-Domain Protein Elk-1
MAP Kinase Kinase 4
Heterotrimeric GTP-Binding Proteins
Terminator Codon
Genistein
Extracellular Signal-Regulated MAP Kinases
Mutant Proteins
Fibroblasts
Protein-Tyrosine Kinases
Substitution reactions
Phosphotransferases
Cells
Cell Line

Keywords

  • Effector mutant
  • Mitogen-activated kinase
  • Src kinase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Adarichev, V. A., Vaiskunaite, R., Niu, J., Balyasnikova, I. V., & Voyno-Yasenetskaya, T. A. (2003). Gα13-mediated transformation and apoptosis are permissively dependent on basal ERK activity. American Journal of Physiology - Cell Physiology, 285(4 54-4).

Gα13-mediated transformation and apoptosis are permissively dependent on basal ERK activity. / Adarichev, Vyacheslav A.; Vaiskunaite, Rita; Niu, Jiaxin; Balyasnikova, Irina V.; Voyno-Yasenetskaya, Tatyana A.

In: American Journal of Physiology - Cell Physiology, Vol. 285, No. 4 54-4, 01.10.2003.

Research output: Contribution to journalArticle

Adarichev, VA, Vaiskunaite, R, Niu, J, Balyasnikova, IV & Voyno-Yasenetskaya, TA 2003, 'Gα13-mediated transformation and apoptosis are permissively dependent on basal ERK activity', American Journal of Physiology - Cell Physiology, vol. 285, no. 4 54-4.
Adarichev VA, Vaiskunaite R, Niu J, Balyasnikova IV, Voyno-Yasenetskaya TA. Gα13-mediated transformation and apoptosis are permissively dependent on basal ERK activity. American Journal of Physiology - Cell Physiology. 2003 Oct 1;285(4 54-4).
Adarichev, Vyacheslav A. ; Vaiskunaite, Rita ; Niu, Jiaxin ; Balyasnikova, Irina V. ; Voyno-Yasenetskaya, Tatyana A. / Gα13-mediated transformation and apoptosis are permissively dependent on basal ERK activity. In: American Journal of Physiology - Cell Physiology. 2003 ; Vol. 285, No. 4 54-4.
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AU - Voyno-Yasenetskaya, Tatyana A.

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