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A target of thrombin activation promotes cell cycle re‐entry by urodele muscle cells
Author(s) -
Tanaka Elly M.,
Brockes Jeremy P.
Publication year - 1998
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.1998.60413.x
Subject(s) - microbiology and biotechnology , thrombin , myogenesis , cell cycle , progenitor cell , retinoblastoma protein , regeneration (biology) , biology , phosphorylation , chemistry , cell , stem cell , myocyte , biochemistry , immunology , platelet
A key early event of newt limb regeneration is the local dedifferentiation of cells to form dividing progenitor cells. This involves the plasticity of differentiation and the ability to re‐enter the cell cycle. In culture, differentiated newt myotubes are able to re‐enter S‐phase in response to serum stimulation. Here, we analyzed the intracellular and extracellular requirements for this process. Cell cycle re‐entry depends on the phosphorylation of the retinoblastoma protein, which is a key regulator of the G1‐S transition. This is in contrast to mammalian myotubes, which are refractory to serum stimulation and cannot phosphorylate retinoblastoma protein in response to serum. The serum factor responsible for this phosphorylation appears to be distinct from common polypeptide growth factors and is enriched in crude preparations of bovine thrombin. Fractionation and analysis of this preparation indicate that the factor is regulated by thrombin and plasmin proteolysis. These results indicate that factors involved in acute responses to wounding such as clotting may be important initiators of the regenerative response.