Recombinant Human FGF9

FGF-9 (fibroblast growth factor-9), also called HBGF-9 (heparin-binding growth factor-9) and GAF (glia-activating factor), is an approximately 26 kDa secreted glycoprotein of the FGF family ^[1-3]. FGFs exhibit heparin-dependent regulation of cell prolifer ation, differentiation, and function, and are characterized by a core heparin-binding FGF domain of approximately 120 amino acids (aa) that exhibits a beta -trefoil structure ^[1]. FGF-9, -16 and -20 form a subfamily that shares 65-71% aa sequence identity, binds FGF R3 (IIIb), and are efficiently secreted despite having an uncleavable, bipartite signal sequence ^[1-3]. Secreted human FGF-9 is a 205-207 aa protein that lacks the N-terminal 1-3 aa and shares 98% sequence identity with mouse, rat, equine, porcine and bovine FGF-9. In addition to FGF R3 (IIIb), FGF-9 binding to the IIIc splice forms of FGF R1, R2 and R3 are variably reported ^[3-5]. An unusual constitutive dimerization of FGF-9 buries receptor interaction sites which lowers its activity and increases heparin affinity which inhibits diffusion ^[4-6]. A spontaneous mouse mutant, Eks, interferes with dimerization, resulting monomeric, diffusible FGF-9 that causes elbow and knee synostoses (joint fusions) due to FGF-9 misexpression in developing joints ^[6]. In humans, FGF-9 mutations that lower receptor binding cause multiple synostoses syndrome (SYNS) ^[7]. Expression in brain and kidney are reported in the adult rat ^{[2, 8]}. In the mouse embryo the location and timing of FGF-9 expression affects development of the skeleton, cerebellum, lungs, heart, vasculature, digestive tract, and testes ^{[1, 6-11]}. Deletion of mouse FGF-9 is lethal at birth due to lung hypoplasia, and causes rhizomelia, or shortening of the proximal skeleton ^{[1, 10, 11]}. Altered FGF-9 expression or function is reported in human colon, endometrial, and ovarian cancers, correlating with progression, invasiveness, and survival ^[12-15]. 

Reference

[1] Itoh, N. and D.M. Ornitz (2008) Dev. Dyn. 237:18.

[2] Miyamoto, M. et al. (1993) Mol. Cell. Biol. 13:4251.

[3] Santos-Ocampo, S. et al. (1996) J. Biol. Chem. 271:1726.

[4] Mohammadi, M. et al. (2005) Cytokine Growth Factor Rev. 16:107.

[5] Plotnikov, A.N. et al. (2001) J. Biol. Chem. 276:4322.

[6] Harada, M. et al. (2009) Nat. Genet. 41:289.

[7] Wu, X.L. et al. (2009) Am. J. Hum. Genet. 85:53.

[8] Colvin, J.S. et al. (1999) Dev. Dyn. 216:72.

[9] Lin, Y. et al. (2009) Dev. Biol. 329:44.

[10] Hung, I.H. et al. (2007) Dev. Biol. 307:300.

[11] Colvin, J.S. et al. (2001) Dev. Dyn 128:2095.

[12] Krejci, P. et al. (2009) Hum. Mutat. 30:1245.

[13] Leushacke, M. et al. (2011) PLoS ONE 6: e23381.

[14] Hendrix, N.D. et al. (2006) Cancer Res. 66:1354.

[15] Abdel-Rahman, W.M. et al. (2008) Hum. Mutat. 29:390.