NGF activates similar intracellular signaling pathways in vascular smooth muscle cells as PDGF-BB but elicits different biological responses

Rosemary Kraemer, Hiep Nguyen, Keith L. March, Barbara Hempstead

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The signaling pathways that regulate smooth muscle cell migration and proliferation are incompletely understood. Smooth muscle cells express at least 3 families of receptor tyrosine kinases that mediate cell migration: platelet-derived growth factor (PDGF) receptors, the trk family of neurotrophin receptors, and insulin-like growth factor 1 receptor. The neurotrophin, nerve growth factor (NGF), and insulin-like growth factor 1 induce the migration but not the proliferation of smooth muscle cells, whereas PDGF-BB stimulates both responses. To determine whether distinct signaling pathways downstream of receptor tyrosine kinases specifically mediate smooth muscle cell migration or proliferation, the ligand-induced activation of different signaling pathways in smooth muscle cells was examined. NGF induces prolonged activation of the Shc/MAP kinase pathway and phospholipase Cγ compared with PDGF-BB. The activation of phosphatidylinositol-3 kinase, however, was 10-fold greater in response to PDGF-BB compared with NGF. Insulin-like growth factor 1 activates only phosphatidylinositol-3 kinase. Pharmacological inhibitors of phosphatidylinositol-3 kinase, Wortmannin and LY294002, inhibit PDGF-BB and NGF-induced migration, whereas an inhibitor of MAP kinase kinase, PD98059, has no effect. Our results suggest that (1) different receptor tyrosine kinases use similar patterns of activation of signaling pathways to mediate distinct biological outcomes of cell migration and proliferation, (2) NGF activates signaling proteins in smooth muscle cells similar to those activated during NGF-induced neuronal differentiation, and (3) the combinatorial effects of different signaling pathways are important for the regulation of smooth muscle cell migration and proliferation. Further studies using mutant trk receptors will help to define the signal transduction pathways mediating NGF-induced smooth muscle cell migration.

Original languageEnglish
Pages (from-to)1041-1050
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number4
StatePublished - Apr 1999

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Nerve Growth Factor
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Movement
Phosphatidylinositol 3-Kinase
Receptor Protein-Tyrosine Kinases
Cell Proliferation
Somatomedins
Neurotrophin 3
Nerve Growth Factor Receptors
Somatomedin Receptors
Platelet-Derived Growth Factor Receptors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
platelet-derived growth factor BB
Mitogen-Activated Protein Kinase Kinases
Nerve Growth Factors
Type C Phospholipases
Signal Transduction
Phosphotransferases
Pharmacology

Keywords

  • Migration
  • Proliferation
  • Signal transduction
  • Smooth muscle cells
  • trk

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

NGF activates similar intracellular signaling pathways in vascular smooth muscle cells as PDGF-BB but elicits different biological responses. / Kraemer, Rosemary; Nguyen, Hiep; March, Keith L.; Hempstead, Barbara.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 19, No. 4, 04.1999, p. 1041-1050.

Research output: Contribution to journalArticle

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