Receptors for fibroblast growth factors.
The recent discovery of the involvement of heparan sulfate proteoglycans (HSPG) in the activation of fibroblast growth factor receptors (FGFR) has led to an intensification of study of this field. It appears that the HSPG act as low affinity receptors to which the fibroblast growth factors (FGF) must bind in order to successfully activate the high affinity FGFR. Heparan sulfate chains consisting of alternately arranged N-acetylated or N-sulfated glucosamine and uronic acid disaccharide regions, covalently attached to a core protein are found in two major families of cell surface HSPG, the syndecans and glypicans. A high affinity bFGF binding region has been isolated from fibroblast HS. There are four basic members of the FGFR family (FGFR 1-4), as well as a wealth of splice variants. The alternative forms of the basic receptors can have altered ligand binding or signalling qualities, depending on the region of the gene which is spliced. Investigations with null FGFR, incapable of signalling, have demonstrated the requirement for FGF in the organization of mammalian tissues and in embryonic patterning. Mutation of the FGFR genes has been recognized recently in human craniosynostoses where a single base pair mutation in the FGFR gene results in skeletal malformations specific to each syndrome. One suggestion is that the interaction of the mutant FGFR with the HSPG/FGF complex somehow contributes to the disease phenotype.
Coutts
J C
JC
CRC Department of Drug Development, Paterson Institute for Cancer Research, Manchester, UK.
Gallagher
J T
JT
D001665:Binding Sites; D005346:Fibroblast Growth Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D011509:Proteoglycans / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D005346:Fibroblast Growth Factors; D006497:Heparan Sulfate; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor