The requirement of Ras and Rap1 for the activation of ERKs by cAMP, PACAP, and KCl in cerebellar granule cells

Yutaro Obara, Angela Horgan, Philip Stork

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

In cerebellar granule cells, the mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) cascade mediates multiple functions, including proliferation, differentiation, and survival. In these cells, ERKs are activated by diverse stimuli, including cyclic adenosine monophosphate (cAMP), pituitary adenylate cyclase activating protein (PACAP), depolarization induced by elevated extracellular potassium (KCl), and the neurotrophin brain-derived neurotrophic factor. Extensive studies in neuronal cell lines have implicated the small G proteins Ras and Rap1 in the activation of ERKs by cAMP, PACAP, and KCl. However, the requirement of Ras and Rap1 in these pathways in cerebellar granule cells has not been addressed. In this study, we utilize multiple biochemical assays to determine the mechanisms of action and requirement of Ras and Rap1 in cultured cerebellar granule cells. We show that both Ras and Rap1 can be activated by cAMP or PACAP via protein kinase (PKA)-dependent mechanisms. KCl activation of Ras also required PKA. Using both adenoviral and transgenic approaches, we show that Ras plays a major role in ERK activation by cAMP, PACAP, and KCl, while Rap1 also mediates activation of a selective membrane-associated pool of ERKs. Furthermore, Rap1, but not Ras, activation by PKA appears to require the action of Src family kinases.

Original languageEnglish (US)
Pages (from-to)470-482
Number of pages13
JournalJournal of Neurochemistry
Volume101
Issue number2
DOIs
StatePublished - Apr 2007

Fingerprint

Adenylyl Cyclases
Cyclic AMP
Chemical activation
Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Proteins
ras Proteins
Monomeric GTP-Binding Proteins
src-Family Kinases
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Mitogen-Activated Protein Kinases
Depolarization
Potassium
Assays
Cell Line
Membranes
Cells

Keywords

  • Cerebellar granular cells
  • Cyclic adenosine monophosphate
  • Extracellular signal-regulated kinase
  • Rap1 GTPase
  • Ras GTPase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

The requirement of Ras and Rap1 for the activation of ERKs by cAMP, PACAP, and KCl in cerebellar granule cells. / Obara, Yutaro; Horgan, Angela; Stork, Philip.

In: Journal of Neurochemistry, Vol. 101, No. 2, 04.2007, p. 470-482.

Research output: Contribution to journalArticle

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