Ras-dependent activation of fibroblast mitogen-activated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit-initiated pathway. Biochemistry 1996 Oct 29;35(43):13716-22
Date
10/29/1996Pubmed ID
8901512DOI
10.1021/bi961764nScopus ID
2-s2.0-0029904963 (requires institutional sign-in at Scopus site) 98 CitationsAbstract
Serotonin (5-HT) is a potent mitogen in many cells types, an action which is frequently mediated through pertussis toxin-sensitive G proteins. In the current study, we used pharmacological inhibitors and dominant negative signaling constructs to delineate elements which participate in the activation of MAPK, a growth-associated mitogen-activated protein kinase, by human G protein-coupled 5-HT1A receptor transfected into CHO-K1 cells in a stable manner. The activation pathway does not directly involve phorbol ester-sensitive protein kinase C types, but does require (i) pertussis toxin-sensitive G protein beta gamma-subunits, (ii) a staurosporine- and genistein-sensitive protein kinase, (iii) phosphoinositide-3'-kinase activity, (iv) activation of Sos in a multimolecular complex that contains p46Shc, and p52Shc, and Grb2, (v) the GTPase p21Ras, and (vi) the protein kinase p74Raf-1. These data demonstrate that the 5-HT1A receptor mediates MAPK activity by convergence upon a common activation pathway that is shared with receptor tyrosine kinases.
Author List
Garnovskaya MN, van Biesen T, Hawe B, CasaƱas Ramos S, Lefkowitz RJ, Raymond JRAuthor
John R. Raymond MD President, CEO, Professor in the President department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular Transport
Animals
CHO Cells
Calcium-Calmodulin-Dependent Protein Kinases
Cricetinae
Enzyme Activation
GRB2 Adaptor Protein
GTP-Binding Proteins
Gene Expression Regulation
Immunoblotting
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
Pertussis Toxin
Precipitin Tests
Protein-Tyrosine Kinases
Proteins
Receptor Protein-Tyrosine Kinases
Receptors, Serotonin
Receptors, Serotonin, 5-HT1
Shc Signaling Adaptor Proteins
Signal Transduction
Src Homology 2 Domain-Containing, Transforming Protein 1
Transfection
Virulence Factors, Bordetella