title: Insulin, thrombine, ERK1/2 kinase and vascular smooth muscle cells proliferation.
abstract: Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerous studies including our own, that ERK1/ERK2 pathway has an important role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMC's proliferation remains poorly understood. Thus, this review examines recent findings in signaling mechanisms involved in INS and thrombin- triggered VSMC's proliferation with particular emphasis on ERK1/2 signaling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.
authors.affiliation: Vinca Institute of Nuclear Sciences, University of Belgrade, Department for Molecular Genetics and Radiobiology, P.O. Box 522, 11001 Belgrade, Serbia.
authors.forename: Esma R
authors.initials: ER
authors.lastname: Isenović
authors.forename: Sanja
authors.initials: S
authors.lastname: Soskić
authors.forename: Andreja
authors.initials: A
authors.lastname: Trpković
authors.forename: Branislava
authors.initials: B
authors.lastname: Dobutović
authors.forename: Milan
authors.initials: M
authors.lastname: Popović
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gluvić
authors.forename: Biljana
authors.initials: B
authors.lastname: Putniković
authors.forename: Pierre
authors.initials: P
authors.lastname: Marche
mesh_terms: D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000201:enzymology; D013917:Thrombin / Q000502:physiology*
chemical_list: D007328:Insulin; D048049:Extracellular Signal-Regulated MAP Kinases; D013917:Thrombin