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GENES CELLS (1998) 3, 125-134.
Copyright © 1998 Blackwell Publishing or its licensors



Original Article

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

A Shimizu, M Kato, A Nakao, T Imamura, P ten Dijke, CH Heldin, M Kawabata, S Shimada, and K Miyazono

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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