Plk1 regulates MEK1/2 and proliferation in airway smooth muscle cells

Respir Res. 2015 Aug 5;16(1):93. doi: 10.1186/s12931-015-0257-8.

Abstract

Background: Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated in the regulation of mitosis. In addition, the activation of mitogen-activated protein kinase (MAPK) is a key event in the early stage of the growth factor response. The role of Plk1 in MAPK phosphorylation in cells has not been investigated.

Methods: Immunoblot analysis was used to evaluate Plk1 and MAPK phosphorylation in cells upon stimulation with platelet-derived growth factor (PDGF). We also generated stable Plk1 knockdown (KD) cells to assess the role of Plk1 in MAPK activation and cell proliferation. Furthermore, we used a non-phosphorylatable Plk1 mutant to determine the function of Plk1 phosphorylation in these processes.

Results: Treatment with PDGF increased Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in human airway smooth muscle cells. Plk1 KD attenuated the PDGF-induced phosphorylation of MEK1/2 and ERK1/2 as well as cell proliferation. However, phosphorylation of Raf-1 and AKT upon stimulation with PDGF was not reduced in Plk1 KD cells. Furthermore, the expression of T210A Plk1 (alanine substitution at Thr-210) inhibited the PDGF-stimulated MEK1/2 phosphorylation, ERK1/2 phosphorylation and cell proliferation.

Conclusions: Together, these findings suggest that Plk1 is activated upon growth factor stimulation, which may control the activation of MEK1/2 and ERK1/2, and smooth muscle cell proliferation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bronchi / cytology
  • Bronchi / physiology
  • Cell Cycle Proteins / physiology*
  • Cell Proliferation / physiology*
  • Humans
  • MAP Kinase Kinase 1 / physiology*
  • MAP Kinase Kinase 2 / physiology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology
  • Myocytes, Smooth Muscle / physiology*
  • Protein-Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Trachea / cytology
  • Trachea / physiology

Substances

  • Cell Cycle Proteins
  • Proto-Oncogene Proteins
  • MAP2K2 protein, human
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • MAP2K1 protein, human