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Ras-dependent activation of fibroblast mitogen-activated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit-initiated pathway.

Publication ,  Journal Article
Garnovskaya, MN; van Biesen, T; Hawe, B; Casañas Ramos, S; Lefkowitz, RJ; Raymond, JR
Published in: Biochemistry
October 29, 1996

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.

Duke Scholars

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

October 29, 1996

Volume

35

Issue

43

Start / End Page

13716 / 13722

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Transfection
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin
  • Receptor Protein-Tyrosine Kinases
  • Proteins
  • Protein-Tyrosine Kinases
 

Citation

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Garnovskaya, M. N., van Biesen, T., Hawe, B., Casañas Ramos, S., Lefkowitz, R. J., & Raymond, J. R. (1996). Ras-dependent activation of fibroblast mitogen-activated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit-initiated pathway. Biochemistry, 35(43), 13716–13722. https://doi.org/10.1021/bi961764n
Garnovskaya, M. N., T. van Biesen, B. Hawe, S. Casañas Ramos, R. J. Lefkowitz, and J. R. Raymond. “Ras-dependent activation of fibroblast mitogen-activated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit-initiated pathway.Biochemistry 35, no. 43 (October 29, 1996): 13716–22. https://doi.org/10.1021/bi961764n.
Garnovskaya MN, van Biesen T, Hawe B, Casañas Ramos S, Lefkowitz RJ, Raymond JR. 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.
Garnovskaya, M. N., et al. “Ras-dependent activation of fibroblast mitogen-activated protein kinase by 5-HT1A receptor via a G protein beta gamma-subunit-initiated pathway.Biochemistry, vol. 35, no. 43, Oct. 1996, pp. 13716–22. Pubmed, doi:10.1021/bi961764n.
Garnovskaya MN, van Biesen T, Hawe B, Casañas Ramos S, Lefkowitz RJ, Raymond JR. 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):13716–13722.
Journal cover image

Published In

Biochemistry

DOI

ISSN

0006-2960

Publication Date

October 29, 1996

Volume

35

Issue

43

Start / End Page

13716 / 13722

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Transfection
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Signal Transduction
  • Shc Signaling Adaptor Proteins
  • Receptors, Serotonin, 5-HT1
  • Receptors, Serotonin
  • Receptor Protein-Tyrosine Kinases
  • Proteins
  • Protein-Tyrosine Kinases