Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts without activation of mitogen-activated protein kinases.
Activin A stimulated DNA synthesis and transient c-fos expression in quiescent Swiss 3T3 fibroblasts. The activin A-induced DNA synthesis was dose-dependent with a half-maximal effect obtained at 0.3 nM. The maximal response obtained at 10 nM was comparable with that induced by 5 ng/ml basic fibroblast growth factor. Swiss 3T3 fibroblasts expressed abundant high affinity binding sites for 125I-labeled activin A with a Kd value of 0.63 nM and the number of binding sites at 24,000/cell. Northern blot analysis revealed that Swiss 3T3 fibroblasts express a high level of type II activin receptor mRNA. In an attempt to elucidate the mechanism of mitogenic action of activin A, we examined the effect of activin A on mitogen-activated protein kinase activation. Unexpectedly, however, activin A did not induce kinase activation under conditions in which basic fibroblast growth factor and endothelin-1 at similar or even less potent mitogenic concentrations did. Furthermore, activin A did not induce phosphorylation of the Erk2 species of mitogen-activated protein kinase. These observations strongly suggest that the activation of mitogen-activated protein kinase is not a necessary step for activin A-induced DNA synthesis in Swiss 3T3 fibroblasts.
Sakurai
T
T
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Abe
Y
Y
Kasuya
Y
Y
Takuwa
N
N
Shiba
R
R
Yamashita
T
T
Endo
T
T
Goto
K
K
D016475:3T3 Cells; D028341:Activins; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D006133:Growth Substances / Q000494:pharmacology*; D007265:Inhibins / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D006133:Growth Substances; D028341:Activins; D007265:Inhibins; D004247:DNA; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1