Genes Cells 1998 Feb 01;32:125-34. doi: 10.1046/j.1365-2443.1998.00174.x.

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

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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.

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Species referenced: Xenopus
Genes referenced: ncoa3 smad10 smad2 smad3 smad4