Endothelin-1, but not Ang II, activates MAP kinases through c-Src independent Ras-Raf dependent pathways in vascular smooth muscle cells. 2007

A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
Kidney Research Centre, University of Ottawa/Ottawa Health Research Institute, 451 Smyth Rd, Ottawa, ON, KIH 8M5.

OBJECTIVE Endothelin-1 (ET-1) and angiotensin II (Ang II) activate common signaling pathways to promote changes in vascular reactivity, remodeling, inflammation, and oxidative stress. Here we sought to determine whether upstream regulators of mitogen-activated protein kinases (MAPKs) are differentially regulated by ET-1 and Ang II focusing on the role of c-Src and the small GTPase Ras. RESULTS Mesenteric vascular smooth muscle cells (VSMCs) from mice with different disruption levels in the c-Src gene (c-Src(+/-) and c-Src(-/-)) and wild-type (c-Src(+/+)) were used. ET-1 and Ang II induced extracellular signal-regulated kinase (ERK) 1/2, SAPK/JNK, and p38MAPK phosphorylation in c-Src(+/+) VSMCs. In VSMCs from c-Src(+/-) and c-Src(-/-), Ang II effects were blunted, whereas c-Src deficiency had no effect in ET-1-induced MAPK activation. Ang II but not ET-1 induced c-Src phosphorylation in c-Src(+/+) VSMCs. Activation of c-Raf, an effector of Ras, was significantly increased by ET-1 and Ang II in c-Src(+/+) VSMCs. Ang II but not ET-1-mediated c-Raf phosphorylation was inhibited by c-Src deficiency. Knockdown of Ras by siRNA inhibited both ET-1 and Ang II-induced MAPK phosphorylation. CONCLUSIONS Our data indicate differential regulation of MAPKs by distinct G protein-coupled receptors. Whereas Ang II has an obligatory need for c-Src, ET-1 mediates its actions through a c-Src-independent Ras-Raf-dependent pathway for MAPK activation. These findings suggest that Ang II and ET-1 can activate similar signaling pathways through unrelated mechanisms. MAP kinases are an important point of convergence for Ang II and ET-1.

UI MeSH Term Description Entries
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000081247 CSK Tyrosine-Protein Kinase Protein tyrosine kinases that phosphorylate tyrosine residues located in the C-terminal tails of SRC-FAMILY KINASES. C-Terminal Src Kinase,Carboxy-Terminal Src Kinase,Protein Tyrosine Kinase p50(csk),Protein-Tyrosine Kinase C-Terminal Src Kinase,Protein-Tyrosine Kinase c-src,Tyrosine Protein Kinase p50csk,Tyrosine-Protein Kinase CSK,c-src Kinase,c-src Tyrosine Kinase,CSK-src,p50(csk),C Terminal Src Kinase,CSK Tyrosine Protein Kinase,CSK src,CSK, Tyrosine-Protein Kinase,Carboxy Terminal Src Kinase,Kinase CSK, Tyrosine-Protein,Kinase c-src, Protein-Tyrosine,Kinase, C-Terminal Src,Kinase, CSK Tyrosine-Protein,Kinase, Carboxy-Terminal Src,Kinase, c-src,Kinase, c-src Tyrosine,Protein Tyrosine Kinase C Terminal Src Kinase,Protein Tyrosine Kinase c src,Src Kinase, C-Terminal,Src Kinase, Carboxy-Terminal,Tyrosine Kinase, c-src,Tyrosine Protein Kinase CSK,Tyrosine-Protein Kinase, CSK,c src Kinase,c src Tyrosine Kinase,c-src, Protein-Tyrosine Kinase
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019061 src-Family Kinases A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes. Protein-Tyrosine Kinases, src,Src Family Tyrosine Kinase,src Kinase,src Kinases,src Tyrosine Kinase,src-Family Kinase,src-Family Tyrosine Kinase,src Tyrosine Kinases,src-Family Tyrosine Kinases,Kinase, src,Kinase, src Tyrosine,Kinase, src-Family,Kinase, src-Family Tyrosine,Kinases, src,Kinases, src Protein-Tyrosine,Kinases, src Tyrosine,Tyrosine Kinase, src,Tyrosine Kinase, src-Family,Tyrosine Kinases, src,Tyrosine Kinases, src-Family,src Family Kinase,src Family Kinases,src Family Tyrosine Kinases,src Protein-Tyrosine Kinases
D019332 Endothelin-1 A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63) Big Endothelin,Big Endothelin-1,Endothelin Type 1,Endothelin, Big,Preproendothelin,Preproendothelin-1,Proendothelin (1-38),Proendothelin-1 Precursor,Big Endothelin 1,Endothelin 1,Endothelin-1, Big,Precursor, Proendothelin-1,Preproendothelin 1,Proendothelin 1 Precursor
D020559 Monomeric GTP-Binding Proteins A class of monomeric, low molecular weight (20-25 kDa) GTP-binding proteins that regulate a variety of intracellular processes. The GTP bound form of the protein is active and limited by its inherent GTPase activity, which is controlled by an array of GTPase activators, GDP dissociation inhibitors, and guanine nucleotide exchange factors. This enzyme was formerly listed as EC 3.6.1.47 G-Proteins, Monomeric,GTP-Binding Proteins, Monomeric,Monomeric G-Protein,Monomeric G-Proteins,Small G-Protein,Small G-Proteins,Small GTPase,Small GTPases,ras-Related GTP-Binding Protein,ras-Related GTPase,ras-Related GTPases,ras-Related G-Proteins,ras-Related GTP-Binding Proteins,G Proteins, Monomeric,G-Protein, Monomeric,G-Protein, Small,G-Proteins, Small,G-Proteins, ras-Related,GTP Binding Proteins, Monomeric,GTP-Binding Protein, ras-Related,GTP-Binding Proteins, ras-Related,GTPase, Small,GTPase, ras-Related,GTPases, Small,GTPases, ras-Related,Monomeric G Protein,Monomeric G Proteins,Monomeric GTP Binding Proteins,Protein, ras-Related GTP-Binding,Proteins, ras-Related GTP-Binding,Small G Protein,Small G Proteins,ras Related G Proteins,ras Related GTP Binding Protein,ras Related GTP Binding Proteins,ras Related GTPase,ras Related GTPases

Related Publications

A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
June 2004, Journal of hypertension,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
January 1998, Pulmonary pharmacology & therapeutics,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
July 1999, Hypertension research : official journal of the Japanese Society of Hypertension,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
May 2013, Biochimica et biophysica acta,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
September 1996, Nature,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
December 2016, International journal of molecular medicine,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
December 1995, Circulation research,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
April 1999, Oncogene,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
January 2005, Lung,
A Yogi, and G E Callera, and A C I Montezano, and A B Aranha, and R C Tostes, and E L Schiffrin, and R M Touyz
January 2007, Current vascular pharmacology,
Copied contents to your clipboard!