Genome-wide comparison of FGFRL1 with structurally related surface receptors

Abstract

FGFRL1 (FGFR5) is a member of the fibroblast growth factor receptor family, which lacks the intracellular tyrosine kinase domain required for signal transduction by trans-phosphorylation. Since it still contains a cytoplasmic domain of 100 amino acid residues with a peculiar histidine-rich element, it might be involved in an alternative pathway of downstream signaling. To get a clue about a possible mechanism, we compared the overall structure of FGFRL1 with all proteins from the UniProt databank. We found that the human genome encodes 42 structurally related proteins with a signal peptide, three Ig-like domains and a transmembrane domain. These proteins can be grouped in seven families, fibroblast growth factor receptors (FGFRs), Fc receptor-like proteins, IL-1 receptor-like proteins, killer cell Ig-like receptors (KIRs), nectin-like proteins, sialic acid binding lectins (SIGLECs) and signal regulatory proteins (SIRPs). The 7 families utilize four different strategies for signaling, namely a protein tyrosine kinase domain, a TIR (Toll/IL-1 receptor) domain, ITIM/ITAM motifs as well as carboxy-terminal peptides that interact with the PDZ domain of an adaptor protein. It remains to be determined whether FGFRL1 might also utilize one of these strategies for signaling.