Orest W. Blaschuk

Fibroblast growth factor receptors contain a conserved HAV region common to cadherins and influenza strain a hemagglutinins: A role in protein-protein interactions?

The first extracellular domain of the cadherins has been shown to exhibit extensive sequence homology with the amino termini of the HA1 chains of influenza strain A hemagglutinins. These regions of homology are known to be functionally important in both the cadherins and the hemagglutinins. The homologous regions harbor the tripeptide HAV, which has been identified as being the cadherin cell adhesion recognition sequence. Here we report that members of the rapidly expanding family of fibroblast growth factor receptors also possess HAV-containing regions. These regions are homologous to the HAV-containing regions present within both the hemagglutinins and the cadherins and appear to be involved in regulating the function of the fibroblast growth factor receptors. We speculate that the HAV motif may represent an evolutionarily conserved amino acid sequence that will prove to be functionally important in a wide variety of proteins.

Cadherins and Ovarian Follicular Development

The cadherins are a family of integral membrane glycoproteins that mediate calcium-dependent cell adhesion (1). We have shown that granulosa cells from diethylstilbesterol (DES)-primed immature rats adhere to one another in a calcium-dependent manner and express a cadherin that is related to murine E-cadherin (2, 3). Disaggregated rat granulosa cells do not express cadherin (2) and are incapable of FSH-stimulated LH receptor induction in vitro (4). The inclusion of estradiol with FSH in cultures of disaggregated rat granulosa cells restores cadherin expression (3), promotes cell aggregation (3, 4), and re-establishes FSH-stimulated LH receptor induction (2, 4). These observations suggest that cadherin-mediated cell aggregation may be necessary for FSH-stimulated LH-receptor induction in granulosa cells. We have tested this possibility in two ways.