Fibroblast Growth Factor 9 (FGF-9)

First printed in R&D Systems' 1996 Catalog.


Consistent with their names, most FGFs initiate fibroblast proliferation. This has been demonstrated for FGFs 1 - 6, plus 8 and 9.1-8 However, the general FGF designation is clearly limiting by its description of one target cell and one biological activity. For instance the original FGF molecule (now known as FGF-2 or FGF basic) also induces proliferation of endothelial cells, chondrocytes, smooth muscle cells, and melanocytes, etc.2 Furthermore, the FGF-2 molecule has been shown to be more than a growth factor. It induces adipocyte differentiation, stimulates astrocyte migration and prolongs neuron survival.2,9 Since this pattern of variable in vitro effects is repeated throughout the family, it may be more appropriate to consider these molecules physiological regulators rather than simple growth factors. To date, the FGF family includes nine members (FGF-1 - 9), all of which are characterized by an internal 120 amino acid sequence that allows for growth factor binding to cell surface receptors.5,10,11 Four distinct receptor genes have been positively identified for the FGFs. Multiple receptor isoforms can be generated from these genes by alternative splicing and cross-reactivities have been demonstrated for multiple family members. This accounts for the identical effects generated by many FGF molecules on common cell types.10,12 The FGFs, partly by way of their originally recognized proliferative activities, are now considered to play substantial roles in development, tissue remodeling, hematopoiesis, and tumorigenesis.

Structural Information

In general, the native molecular masses of the FGFs range from 17 kDa to 38 kDa. Acknowledging some uncertainty in signal peptide cleavage sites, plus the existence of alternative splice variants, mature FGF amino acid (aa) lengths range from 155 aa residues to 267 aa residues.6,11,13-21 FGF-8, is a 28-32 kDa glycoprotein that has only been identified in mouse and differs from the other FGFs by the absence of a highly conserved cysteine.22 Over the entire coding sequence, aa identity among the eight human FGFs, relative to the shortest (155 aa) molecule, is 14%. Over a conserved internal stretch of approximately 112 aa residues, the identity rises to 17%.4,13 Considerable species cross-reactivity has been reported for FGF-1 - 7 and 9, with studies on FGF-8 having been limited to the mouse.3,6,13,18,20,23,24 FGF-9: FGF-9, or glia-activating factor, was initially discovered in the medium of the human NMC-G1 glioma cell line. Although it contains no identifiable signal sequence (except for the first three amino acids), it is clearly secreted, presumably via an alternative secretory path-way8,13 The secreted native molecule exists as a single chain, heparin-binding glycosylated polypeptide of approximately 30 kDa that is 208 aa residues in length. Human FGF-9 shows 32% sequence identity to human FGF-2, and the molecule is conserved across species as rat FGF-9 is 94% identical to human FGF-913 Although FGF-9 shows a mitogenic effect on fibroblasts, it is somewhat unusual among FGFs in that it has no effect on endothelial cells, a property shared with FGF-715 and FGF-6 (which has a very limited activity on endothelium).5 To date, a mitogenic effect of FGF-3 on endothelium has not been reported either. Cells known to express FGF-9 have not been determined, however, general transcripts for the molecule have been identified in brain and kidney.13

High-Affinity Receptors

To date, four distinct genes have been identified which code for multiple, alternatively spliced FGF receptors (FGFR1-4).10,12 Although the exact receptor(s) for FGF-9 has not been determined, it would appear unlikely that it is FGFR1, since this receptor is expressed on endothelial cells and endothelial cells are unresponsive to FGF-9.26

Biological Activity

Virtually nothing is known about FGF-9 activity in vitro. It is known to induce proliferation of fibroblasts and type I astrocytes in vitro and will induce transformation of fibroblasts when transfected into a 3T3 cell line.13


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