Identification of receptors and Smad proteins involved in activin signalling in a human epidermal keratinocyte cell line.
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.
Shimizu
A
A
Department of Biochemistry, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo.
Kato
M
M
Nakao
A
A
Imamura
T
T
ten Dijke
P
P
Heldin
C H
CH
Kawabata
M
M
Shimada
S
S
Miyazono
K
K
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism
D004268:DNA-Binding Proteins; D017978:Receptors, Growth Factor; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D029404:Activin Receptors