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Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line
Author(s) -
Shimizu Akira,
Kato Mitsuyasu,
Nakao Atsuhito,
Imamura Takeshi,
Ten Dijke Peter,
Heldin CarlHenrik,
Kawabata Masahiro,
Shimada Shinji,
Miyazono Kohei
Publication year - 1998
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1998.00174.x
Subject(s) - hacat , activin type 2 receptors , acvr2b , smad , activin receptor , biology , smad2 protein , microbiology and biotechnology , r smad , tgf beta signaling pathway , receptor , phosphorylation , endoglin , signal transduction , transforming growth factor , cell culture , epidermal growth factor , tgf alpha , biochemistry , genetics , stem cell , cd34
Background: Activin A is a multifunctional protein, which is a member of the transforming growth factor‐β (TGF‐β) superfamily. Smad proteins have recently been shown to transduce signals for the TGF‐β 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‐β induced an efficient phosphorylation of both Smad2 and Smad3. Activin A preferentially induced the nuclear translocation of Smad3 in HaCaT cells, whereas TGF‐β 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.