title: MHC class I and integrin ligation induce ERK activation via an mTORC2-dependent pathway.
abstract: The aim of this study was to characterize the interaction between mTOR and ERK in primary endothelial cells (EC) following MHC class I and integrin ligation. Ligation of MHC class I molecules or integrins on the surface of EC leads to phosphorylation of ERK at Thr202/Tyr204. We utilized small interfering RNA (siRNA) blockade of mTOR and proteins involved in mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) to define a relationship between mTOR and ERK following MHC class I signaling. We found mTORC2 was responsible for MHC class I and integrin induced phosphorylation of ERK at Thr202/Tyr204. We corroborated these results demonstrating that long-term exposure to rapamycin also inhibited ERK pathway activation in response to MHC class I signaling. Our results demonstrate, for the first time, that engagement of either MHC class I or integrin on the surface of EC leads to ERK activation through an mTORC2-dependent pathway.
authors.affiliation: UCLA Immunogenetics Center, David Geffen School of Medicine UCLA, 1000 Veteran Avenue Los Angeles, CA 90095, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Jindra
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Jin
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jacamo
authors.forename: Enrique
authors.initials: E
authors.lastname: Rozengurt
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
chemical_list: D015234:HLA-A Antigens; D016023:Integrins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases