F. Wang et al., A HOMEO-INTERACTION SEQUENCE IN THE ECTODOMAIN OF THE FIBROBLAST GROWTH-FACTOR RECEPTOR, The Journal of biological chemistry, 272(38), 1997, pp. 23887-23895
Interaction of fibroblast growth factor receptors (FGFR) sufficient fo
r a trans-phosphorylation event in which one intracellular domain is s
ubstrate for the other is essential for signal transduction. By analys
is of the direct interaction of recombinant constructions coexpressed
in baculoviral-infected insect cells, we identified a 17-amino acid se
quence that is required for the stable interaction between ectodomains
of FGFR, The sequence (160)ERSPHRPILQAGLPANK(176) (Glu(160)-Lys(176))
connects immunoglobulin modules II and III. In insect cells, the inte
raction between Glu(160)-Lys(176) domains occurs independently of inta
ct heparin or FGF binding domains, The sequence is not required for th
e binding of heparin or FGF-1, but is essential for mitogenic activity
of the FGFR kinase in mammalian cells. The results support a model in
which the homeo-interaction between Glu(160)-Lys(176) in the ectodoma
in contributes to the interaction between intracellular domains in mam
malian cell membranes (Kan, M., Wang, F., Kan, M., To, B., Gabriel, J.
L., and McKeehan, W. L. (1996) J. Biol. Chem. 271, 26143-26148), We p
ropose that the Glu(160)-Lys(176) domain plays a pivotal role in restr
iction of the interaction between kinases by pericellular matrix hepar
an sulfate proteoglycan and divalent cations. Restrictions are overcom
e by FGF or constitutively by diverse gain of function mutations which
cause skeletal and craniofacial abnormalities.