Thrombin cleaves the high molecular weight forms of basic fibroblast growth factor (FGF-2): a novel mechanism for the control of FGF-2 and thrombin activity.
The fgf-2 gene encodes low molecular weight (LMW, 18 kDa) and high molecular weight (HMW, 22-24 kDa) forms that originate from alternative translation of a single mRNA and exhibit diverse biological functions. HMW fibroblast growth factor-2 (FGF-2) inhibits cell migration and induces cell transformation or growth arrest in a cell type- and dose-dependent fashion. Conversely, LMW FGF-2 upregulates both cell proliferation and migration in most cell types. Although transcriptional and translational regulation of HMW and LMW FGF-2 has been extensively investigated, little is known about post-translational control of their relative expression. Here we report that thrombin, a key coagulation factor and inflammatory mediator, cleaves HMW FGF-2 into an LMW FGF-2-like form that stimulates endothelial cell migration and proliferation. The effect of thrombin on these cell functions requires HMW FGF-2 cleavage. This post-translational control mechanism adds a novel level of complexity to the regulation of FGF-2, and links the activities of thrombin and FGF-2 in patho-physiological processes in which both molecules are expressed.
Yu
P-J
PJ
Department of Cardiothoracic Surgery, The Seymour Cohn Cardiovascular Research Laboratory, New York University School of Medicine, New York, NY 10016, USA.
Ferrari
G
G
Pirelli
L
L
Galloway
A C
AC
Mignatti
P
P
Pintucci
G
G
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology
D018836:Inflammation Mediators; D016222:Fibroblast Growth Factor 2; D013917:Thrombin