Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic smooth muscle

Ilia A. Yamboliev, Kevin M. Wiesmann, Cherie A. Singer, Jason Hedges, William T. Gerthoffer

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In canine colon, M2/M3 muscarinic receptors are coupled to extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. We tested the hypothesis that this coupling is mediated by enzymes of the phosphatidylinositol (PI) 3-kinase family. RT-PCR and Western blotting demonstrated expression of two isoforms, PI 3-kinase-α and PI 3-kinase-γ. Muscarinic stimulation of intact muscle strips (10 μM ACh) activated PI 3-kinase-γ, ERK and p38 MAP kinases, and MAP kinase-activated protein kinase-2, whereas PI 3-kinase-α activation was not detected. Wortmannin (25 μM) abolished the activation of PI 3-kinase-γ ERK, and p38 MAP kinases. MAP kinase inhibition was a PI 3-kinase-γ-specific effect, since wortmannin did not inhibit recombinant activated murine ERK2 MAP kinase, protein kinase C, Raf-1, or MAP kinase kinase. In cultured muscle cells, newborn calf serum (3%) activated PI 3-kinase-α and PI 3-kinase-γ isoforms, ERK and p38 MAP kinases, and stimulated chemotactic cell migration. Using wortmannin and LY-294002 to inhibit PI 3-kinase activity and PD-098059 and SB-203580 to inhibit ERK and p38 MAP kinases, we established that these enzymes are functionally important for regulation of chemotactic migration of colonic myocytes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number2 48-2
StatePublished - 2000
Externally publishedYes

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Phosphatidylinositol 3-Kinase
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Phosphatidylinositol 3-Kinases
Smooth Muscle
Muscle
Canidae
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase Kinases
Muscle Cells
Protein Isoforms
Chemical activation
Proto-Oncogene Proteins c-raf
Muscarinic M3 Receptors
Muscarinic M2 Receptors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Enzymes
Protein Kinases
Protein Kinase C
Cholinergic Agents

Keywords

  • Cell migration
  • Mitogen-activated protein kinases
  • Muscarinic receptors
  • Phosphatidylinositol 3-kinases
  • Reverse transcriptase-polymerase chain reaction

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic smooth muscle. / Yamboliev, Ilia A.; Wiesmann, Kevin M.; Singer, Cherie A.; Hedges, Jason; Gerthoffer, William T.

In: American Journal of Physiology - Cell Physiology, Vol. 279, No. 2 48-2, 2000.

Research output: Contribution to journalArticle

Yamboliev, Ilia A. ; Wiesmann, Kevin M. ; Singer, Cherie A. ; Hedges, Jason ; Gerthoffer, William T. / Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic smooth muscle. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 279, No. 2 48-2.
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