The heparin-binding (fibroblast) growth factor family of receptors (HBGF-R) currently consists of four cloned genes which are expressed as a plethora of isoforms as a consequence of alternate splicing and post-translational modifications. Splice variants can be grouped into those resulting in structural variants in the NH2-terminal domain (extracellular domain of transmembrane isoforms), the intracellular juxtamembrane and the COOH-terminal tyrosine kinase domain. The HBGF-R gene family is characterized by an exceptionally long intracellular juxtamembrane sequence which contains a potential variation in a threonine phosphorylation site for protein kinase C or other kinases between the transmembrane sequence and the first kinase consensus sequence. A potentially novel 34 kilodalton (kDa) protein (p34) has been identified which may bind to the juxtamembrane sequence. The structure of p34 will be deduced from cDNA, recombinant p34 will be expressed in appropriate systems and the nature of the HBGF-R binding domain determined. Modification of p34 binding to HBGF-R by phosphorylation in the juxtamembrane will be tested. The hypothesis that p34 may represent a signal transduction pathway for HBGF-R distinct from conventional SH2-domain substrates (phospholipase C-gamma, GAP, Src, etc. ) will be tested. A homologue of the HBGF-R(Flg) gene has been identified and partially sequenced. Current open reading frames predict that the gene may code for distinct subdomains of full-length HBGF-R(Flg) receptor isoforms. The full-length cDNA for the gene will be determined and the translation products will be characterized. The hypothesis will be tested that distinct subdomain translation products play a role as antagonists of the full-length receptor, in particular potential intracellular activities of receptor isoforms that are not translocated to the cell membrane.