B-Raf-dependent regulation of the MEK-1/mitogen-activated protein kinase pathway in PC12 cells and regulation by cyclic AMP

Richard Vaillancourt, Anne M. Gardner, Gary L. Johnson

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Growth factor receptor tyrosine kinase regulation of the sequential phosphorylation reactions leading to mitogen-activated protein (MAP) kinase activation in PC12 cells has been investigated. In response to epidermal growth factor, nerve growth factor, and platelet-derived growth factor, B- Raf and Raf-1 are activated, phosphorylate recombinant kinase-inactive MEK- 1, and activate wild-type MEK-1. MEK-1 is the dual-specificity protein kinase that selectively phosphorylates MAP kinase on tyrosine and threonine, resulting in MAP kinase activation. B-Raf and Raf-1 are growth factor- regulated Raf family members which regulate MEK-1 and MAP kinase activity in PC12 cells. Protein kinase A activation in response to elevated cyclic AMP (cAMP) levels inhibited B-Raf and Raf-1 stimulation in response to growth factors. Ras·GTP loading in response to epidermal growth factor, nerve growth factor, or platelet-derived growth factor was unaffected by protein kinase A activation. Even though elevated cAMP levels inhibited Raf activation, the growth factor activation of MEK-1 and MAP kinase was unaffected in PC12 cells. The results demonstrate that tyrosine kinase receptor activation of MEK-1 and MAP kinase in PC12 cells is regulated by B- Raf and Raf-1, whose activation is inhibited by protein kinase A, and MEK activators, whose activation is independent of cAMP regulation.

Original languageEnglish (US)
Pages (from-to)6522-6530
Number of pages9
JournalMolecular and Cellular Biology
Volume14
Issue number10
StatePublished - Oct 1994
Externally publishedYes

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PC12 Cells
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Intercellular Signaling Peptides and Proteins
Nerve Growth Factor
Epidermal Growth Factor
MAP Kinase Kinase Kinase 1
Proto-Oncogene Proteins c-sis
Growth Factor Receptors
Platelet-Derived Growth Factor
Receptor Protein-Tyrosine Kinases
Threonine
Protein-Tyrosine Kinases
Protein Kinases
Tyrosine
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

B-Raf-dependent regulation of the MEK-1/mitogen-activated protein kinase pathway in PC12 cells and regulation by cyclic AMP. / Vaillancourt, Richard; Gardner, Anne M.; Johnson, Gary L.

In: Molecular and Cellular Biology, Vol. 14, No. 10, 10.1994, p. 6522-6530.

Research output: Contribution to journalArticle

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