PMID- 27663077 OWN - NLM STAT- MEDLINE DCOM- 20171117 LR - 20181113 IS - 1872-8057 (Electronic) IS - 0303-7207 (Print) IS - 0303-7207 (Linking) VI - 439 DP - 2017 Jan 5 TI - Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LbetaT2 cells. PG - 346-353 LID - S0303-7207(16)30386-0 [pii] LID - 10.1016/j.mce.2016.09.021 [doi] AB - The mammalian target of rapamycin (mTOR) assembles into two different multi-protein complexes, mTORC1 and mTORC2. The mTORC2 complex is distinct due to the unique expression of the specific core regulatory protein Rictor (rapamycin-insensitive companion of mTOR). mTORC2 has been implicated in regulating actin cytoskeletal reorganization but its role in gonadotrope function is unknown. Using the gonadotrope-derived LbetaT2 cell line, we find that the GnRH agonist buserelin (GnRHa) phosphorylates both mTOR and Rictor. Interestingly, inhibition of mTORC2 blunts GnRHa-induced cyto-architectural rearrangements. Coincident with blunting of actin reorganization, inhibition of mTORC2 also attenuates GnRHa-mediated activation of both protein kinase C (PKC) and extracellular signal regulated kinase (ERK). Collectively, our data suggests that GnRHa-mediated mTORC2 activation is important in facilitating actin reorganization events critical for initiating PKC activity and subsequent ERK phosphorylation in the gonadotrope-derived LbetaT2 cell line. CI - Copyright A(c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Edwards, Brian S AU - Edwards BS AD - Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. Electronic address: b80@uwyo.edu. FAU - Isom, William J AU - Isom WJ AD - Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. Electronic address: wyoisom@gmail.com. FAU - Navratil, Amy M AU - Navratil AM AD - Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA. Electronic address: anavrati@uwyo.edu. LA - eng GR - P20 GM103432/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160920 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (Actins) RN - 0 (Carrier Proteins) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Actins/*metabolism MH - Carrier Proteins/*metabolism MH - Enzyme Activation/drug effects MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Gonadotrophs/drug effects/*metabolism MH - Gonadotropin-Releasing Hormone/metabolism/*pharmacology MH - Mechanistic Target of Rapamycin Complex 2/*metabolism MH - Phosphorylation/drug effects MH - Protein Kinase C/metabolism PMC - PMC5123956 MID - NIHMS819997 OTO - NOTNLM OT - Actin OT - ERK OT - Gonadotrope OT - Mammalian target of rapamycin complex 2 OT - PKC EDAT- 2016/09/25 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/01/05 CRDT- 2016/09/25 06:00 PHST- 2016/07/01 00:00 [received] PHST- 2016/08/26 00:00 [revised] PHST- 2016/09/19 00:00 [accepted] PHST- 2016/09/25 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2016/09/25 06:00 [entrez] PHST- 2018/01/05 00:00 [pmc-release] AID - S0303-7207(16)30386-0 [pii] AID - 10.1016/j.mce.2016.09.021 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2017 Jan 5;439:346-353. doi: 10.1016/j.mce.2016.09.021. Epub 2016 Sep 20.