title: Akt-dependent cell size regulation by the adhesion molecule on glia occurs independently of phosphatidylinositol 3-kinase and Rheb signaling.
abstract: The role of cell adhesion molecules in mediating interactions with neighboring cells and the extracellular matrix has long been appreciated. More recently, these molecules have been shown to modulate intracellular signal transduction cascades critical for cell growth and proliferation. Expression of adhesion molecule on glia (AMOG) is downregulated in human and mouse gliomas, suggesting that AMOG may be important for growth regulation in the brain. In this report, we examined the role of AMOG expression on cell growth and intracellular signal transduction. We show that AMOG does not negatively regulate cell growth in vitro or in vivo. Instead, expression of AMOG in AMOG-deficient cells results in a dramatic increase in cell size associated with protein kinase B/Akt hyperactivation, which occurs independent of phosphatidylinositol 3-kinase activation. AMOG-mediated Akt phosphorylation specifically activates the mTOR/p70S6 kinase pathway previously implicated in cell size regulation, but it does not depend on tuberous sclerosis complex/Ras homolog enriched in brain (Rheb) signaling. These data support a novel role for a glial adhesion molecule in cell size regulation through selective activation of the Akt/mTOR/S6K signal transduction pathway.
authors.affiliation: Department of Neurology, Washington University School of Medicine, Box 8111, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Scheidenhelm
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cresswell
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Haipek
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Fleming
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mercer
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000251:Adenosine Triphosphatases; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D027682:Cation Transport Proteins; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D000076205:Ras Homolog Enriched in Brain Protein; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases
chemical_list: D000251:Adenosine Triphosphatases; D027682:Cation Transport Proteins; D015816:Cell Adhesion Molecules, Neuronal; D020559:Monomeric GTP-Binding Proteins; D009479:Neuropeptides; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D000076205:Ras Homolog Enriched in Brain Protein; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000254:Sodium-Potassium-Exchanging ATPase; D058570:TOR Serine-Threonine Kinases; C504190:ATP1B2 protein, human; C504191:Atp1b2 protein, mouse; C490213:Rheb protein, mouse; C546842:MTOR protein, human; C546843:mTOR protein, mouse; C494918:AKT1 protein, human