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1.
P R Health Sci J ; 15(3): 179-86, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8994282

ABSTRACT

Numerous studies have established that stimulation of cell growth by members of the fibroblast growth factor (FGF) family of polypeptides is dependent upon an extracellular pathway. Acidic FGF (FGF-1), however, lacks a classical signal sequence for secretion, thereby making it difficult to evaluate regulation of biological activity by this growth factor. Efforts in this laboratory have utilized molecular techniques of retrovirology and transgenic modeling to introduce cDNA sequences encoding either an intracellular or extracellular form of FGF-1 into primary diploid cells to examine trafficking and compartmentalization of FGF-1. Several lines of evidence obtained from these models provide a compelling argument that the stimulation of FGF-1-associated cellular transformation is restricted to an extracellular, receptor-mediated pathway, involving protein tyrosine phosphorylation and nuclear localization. In addition, an unconventional secretion pathway for intracellular FGF-1 has been identified that involves mechanisms associated with oxidative stress.


Subject(s)
Fibroblast Growth Factor 1/physiology , Neovascularization, Physiologic/drug effects , Signal Transduction/physiology , Animals , Diploidy , Fibroblast Growth Factor 1/chemistry , Gene Expression Regulation , Genetic Vectors , Mice , Mice, Transgenic , Models, Genetic , Phosphorylation , Receptors, Fibroblast Growth Factor/physiology , Tyrosine/metabolism
2.
P. R. health sci. j ; P. R. health sci. j;15(3): 179-86, Sept. 1996.
Article in English | LILACS | ID: lil-228509

ABSTRACT

Numerous studies have established that stimulation of cell growth by members of the fibroblast growth factor (FGF) family of polypeptides is dependent upon an extracellular pathway. Acidic FGF (FGF-1), however, lacks a classical signal sequence for secretion, thereby making it difficult to evaluate regulation of biological activity by this growth factor. Efforts in this laboratory have utilized molecular techniques of retrovirology and transgenic modeling to introduce cDNA sequences encoding either an intracellular or extracellular form of FGF-1 into primary diploid cells to examine trafficking and compartmentalization of FGF-1. Several lines of evidence obtained from these models provide a compelling argument that the stimulation of FGF-1-associated cellular transformation is restricted to an extracellular, receptor-mediated pathway, involving protein tyrosine phosphorylation and nuclear localization. In addition, an unconventional secretion pathway for intracellular FGF-1 has been identified that involves mechanisms associated with oxidative stress


Subject(s)
Animals , Mice , Fibroblast Growth Factor 1/physiology , Neovascularization, Physiologic/drug effects , Signal Transduction/physiology , Diploidy , Fibroblast Growth Factor 1/chemistry , Gene Expression Regulation , Genetic Vectors , Mice, Transgenic , Models, Genetic , Phosphorylation , Receptors, Fibroblast Growth Factor/physiology , Tyrosine/metabolism
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