Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line

Genes Cells. 1998 Feb;3(2):125-34. doi: 10.1046/j.1365-2443.1998.00174.x.

Abstract

Background: Activin A is a multifunctional protein, which is a member of the transforming growth factor-beta (TGF-beta) superfamily. Smad proteins have recently been shown to transduce signals for the TGF-beta superfamily of proteins, and Smad2 was implicated in activin signalling in Xenopus embryos.

Results: We identified the receptors and Smad proteins activated by activin A in a human epidermal keratinocyte cell line, HaCaT. The major activin receptors expressed on HaCaT cells were activin type II receptor (ActR-II) and activin type IB receptor (ActR-IB). We have also shown that in HaCaT cells, activin A induced the phosphorylation of Smad3 and, to a lesser extent, of Smad2. On the other hand, TGF-beta induced an efficient phosphorylation of both Smad2 and Smad3. Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF-beta strongly induced the nuclear translocation of Smad2, as well as other Smads. Moreover, a constitutively active form of ActR-IB efficiently stimulated the formation of a heteromeric complex between Smad3 and Smad4 in COS cells transfected with Smad cDNAs.

Conclusions: These results suggest that activin A binds to a receptor complex of ActR-II and ActR-IB, and preferentially activates Smad3 in HaCaT human keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors
  • Activins
  • Animals
  • COS Cells
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Humans
  • Inhibins / genetics
  • Inhibins / metabolism
  • Keratinocytes / metabolism*
  • Phosphorylation
  • Precipitin Tests
  • Receptors, Growth Factor / metabolism*
  • Signal Transduction*
  • Smad2 Protein
  • Smad3 Protein
  • Trans-Activators*
  • Transfection
  • Transforming Growth Factor beta / metabolism

Substances

  • DNA-Binding Proteins
  • Receptors, Growth Factor
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Activins
  • Inhibins
  • Activin Receptors