Neurotrophin-induced smooth muscle cell migration involves map kinase and phospholipase activation

R. Kraemer, K. March, B. Hempostead

Research output: Contribution to journalArticle

Abstract

Vascular injury results in the migration of medial smooth muscle cells (SMCs) into the intima, followed by their proliferation. We previously demonstrated an increase in expression of neurotrophins and their receptors, the trk family of receptor tyrosine kinases, in vascular lesions. Moreover, nerve growth factor (NGF) is a potent chemotactic agent for vascular SMCs, but does not induce SMC proliferation. The current studies were undertaken to determine if NGF activated similar signaling pathways to mediate SMC migration as compared to those mediating NGF-induced neuronal differentiation. SMCs derived from aortic expiants of a transgenic mouse expressing a temperature sensitive SV40 T antigen, under the control of the SMC o(-actin promoter, were utilized. Cells cultured at 33°C retain a transformed phenotype, but following shift to 39.5°C, acquire differentiated characteristics. Stable clones expressing trk A following cell transaction were cultured at 39.5°C and used for migration and signaling assays. TrkA-mSMC migrated in response to NGF and PDGF, whereas native mSMC only migrated in response to PDGF. PDGF also induced proliferation of trkA-mSMC, but NGF did not. NGF induced a 6-7 fold increase in MAP kinase activity, which persisted for 4 hrs, whereas PDGF-induced MAP kinase activity was transient. NGF or PDGF- induced PLCphosphorylation was similar in duration. This cell system will allow us to analyze the signaling pathways critical for initiating vascular SMC migration.

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996

Fingerprint

nerve growth factor
neurotrophins
Phospholipases
Nerve Growth Factors
Nerve Growth Factor
cell movement
smooth muscle
myocytes
Smooth Muscle Myocytes
Cell Movement
Muscle
phosphotransferases (kinases)
Phosphotransferases
Chemical activation
Cells
blood vessels
Vascular Smooth Muscle
mitogen-activated protein kinase
Polyomavirus Transforming Antigens
Nerve Growth Factor Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Neurotrophin-induced smooth muscle cell migration involves map kinase and phospholipase activation. / Kraemer, R.; March, K.; Hempostead, B.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

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