Format

Send to

Choose Destination
Curr Biol. 1999 Jul 29-Aug 12;9(15):792-9.

Thrombin regulates S-phase re-entry by cultured newt myotubes.

Author information

1
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK.

Abstract

BACKGROUND:

Adult urodele amphibians such as the newt have remarkable regenerative ability, and a critical aspect of this is the ability of differentiated cells to re-enter the cell cycle and lose their differentiated characteristics. Unlike mammalian myotubes, cultured newt myotubes are able to enter and traverse S phase, following serum stimulation, by a pathway leading to phosphorylation of the retinoblastoma protein. The extracellular regulation of this pathway is unknown.

RESULTS:

Like their mammalian counterparts, newt myotubes were refractory to mitogenic growth factors such as the platelet-derived growth factor (PDGF), which act on their mononucleate precursor cells. Cultured newt myotubes were activated to enter S phase by purified thrombin in the presence of subthreshold amounts of serum. The activation proceeded by an indirect mechanism in which thrombin cleaved components in serum to generate a ligand that acted directly on the myotubes. The ligand was identified as a second activity present in preparations of crude thrombin and that was active after removal of all thrombin activity. It induced newt myotubes to enter S phase in serum-free medium, and it acted on myotubes but not on the mononucleate precursor cells. Cultured mouse myotubes were refractory to this indirect mechanism of S-phase re-entry.

CONCLUSIONS:

These results provide a link between reversal of differentiation and the acute events of wound healing. The urodele myotube responds to a ligand generated downstream of thrombin activation and re-enters the cell cycle. Although this ligand can be generated in mammalian sera, the mammalian myotube is unresponsive. These results provide a model at the cellular level for the difference in regenerative ability between urodeles and mammals.

PMID:
10469562
DOI:
10.1016/s0960-9822(99)80362-5
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center