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The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm
A Bhushan1, H Y Lin, H F Lodish
1Molecular Neurobiology Laboratory, Salk Institute, La Jolla, California 92037.
Abstract:
The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells.
Insights
Adding transforming growth factor beta (TGF-beta) type II receptors to Xenopus embryos revealed TGF-beta 1 can induce mesoderm. This suggests TGF-beta and activin signaling pathways are similar, with differences arising from ligand-binding domains.
Area of Science:
- Developmental Biology
- Molecular Signaling
- Cell Biology
Background:
- Type II receptors for transforming growth factor beta (TGF-beta) and activin are serine/threonine protein kinases.
- Activin induces mesodermal cell types in Xenopus animal caps, while TGF-beta 1 has no effect due to absent functional receptors.
Purpose of the Study:
- To investigate the biological activities of TGF-beta 1 by introducing its type II receptor into Xenopus embryos.
- To compare the signaling pathways utilized by TGF-beta and activin.
Main Methods:
- Introduction of RNA encoding the TGF-beta type II receptor into Xenopus embryos.
- Animal cap assays to assess mesoderm induction by TGF-beta 1 and activin.
- Utilizing a dominant inhibitory ras mutant (p21(Asn-17)Ha-ras) to block signaling.
Main Results:
- TGF-beta 1 and activin showed similar potency in inducing mesoderm-specific mRNAs in treated Xenopus embryos.
- Both growth factors elicited the same types of mesodermal tissues.
- The response to both TGF-beta 1 and activin was inhibited by the ras mutant.
Conclusions:
- Activin and TGF-beta type II receptors can utilize similar intracellular signaling pathways.
- The distinct biological effects of TGF-beta and activin are likely due to differences in their ligand-binding domains and cellular responsiveness.