The Heparan Sulfate-Fibroblast Growth Factor Family: Diversity of Structure and Function

Wallace L. McKeehan, Fen Wang, Mikio Kan

Research output: Chapter in Book/Report/Conference proceedingChapter

352 Scopus citations

Abstract

The fibroblast growth factor (FGF) receptor complex is a ubiquitous regulator of development and adult tissue homeostasis that bridges the peri-cellular matrix and the intracellular environment. Diverse members of the FGF polypeptide family, the FGF receptor tyrosine kinase (FGFRTK) family and the FGF receptor heparan sulfate proteoglycan (FGFRHS) family combine to result in active and specific FGFR signal transduction complexes. Regulated alternate splicing and combination of variant subdomains give rise to diversity of FGFRTK monomers. Divalent cations cooperate with the FGFRHS to conformationally restrict FGFRTK trans-phosphorylation, which causes depression of kinase activity and facilitates appropriate activation of the FGFR complex by FGF. Diffusional and conformational molecular models of the oligomeric FGFR complex are presented to explain how different point mutations in the FGFRTK commonly cause craniofacial and skeletal abnormalities of graded severity by graded increases in FGF-independent activity of total FGFR complexes. The role of the FGF family in liver growth and function and in prostate tumor progression is discussed.

Original languageEnglish (US)
Title of host publicationProgress in Nucleic Acid Research and Molecular Biology
Pages135-176
Number of pages42
EditionC
DOIs
StatePublished - Jan 1 1997

Publication series

NameProgress in Nucleic Acid Research and Molecular Biology
NumberC
Volume59
ISSN (Print)0079-6603

ASJC Scopus subject areas

  • Molecular Biology

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