The small peptide OGP(10-14) acts through Src kinases and RhoA pathways in Mo-7e cells: morphologic and immunologic evaluation.
BACKGROUND
Osteogenic growth peptide (OGP) is an endogenous tetradecapeptide present in micromolar concentrations in mammalian serum; its carboxy-terminal pentapeptide, OGP(10-14), represents its physiologically active fragment. OGP(10-14) induces proliferation and differentiation in fibroblast and osteoblast cell lines, and it enhances hematopoiesis in vitro and in vivo. The signaling pathways triggered by OGP(10-14) are not yet fully known. In the present report, we evaluated the effect of OGP(10-14) on differentiation of a cancer megakaryoblast cell line and its involvement on RhoA and Src family kinases signaling pathway.


METHODS
Cell proliferation of the Mo-7e line was evaluated using the MTT test. Mo-7e differentiation was evaluated by microscopic observation of cell morphology and by expression of the factor VIII-related antigen. Involvement of RhoA and Src kinases on signaling pathways triggered by OGP(10-14) was analyzed using RhoA and Src family kinase (SFK) inhibitors (C3 and PP2) and an immunoperoxidase technique.


RESULTS
OGP(10-14) induces expression of the factor VIII-related antigen, morphologic changes indicative of megakaryocytic differentiation, and a down-regulation of the Fyn Src kinase. These OGP(10-14) effects were prevented by C3 and enhanced by PP2.


CONCLUSIONS
The anti-proliferative and pro-differentiating activities of OGP(10-14) on thrombopoietin (TPO)-primed Mo-7e cells are mediated by RhoA and Src kinase pathways as demonstrated by the use of C3 and PP2.
Department of Human Morphology and Applied Biology, Section of Histology and General Embryology, University of Pisa, Via Roma 67, Pisa, Italy.
Letizia
L
Mattii
Barbara
B
Battolla
Stefania
S
Moscato
Rita
R
Fazzi
Sara
S
Galimberti
Nunzia
N
Bernardini
Amelio
A
Dolfi
Mario
M
Petrini
D036002:ADP Ribose Transferases / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006657:Histones / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
C412373:AG 1879; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D011743:Pyrimidines; D014841:von Willebrand Factor; C074533:osteogenic growth peptide; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein