HEPATOMA-DERIVED GROWTH-FACTOR BELONGS TO A GENE FAMILY IN MICE SHOWING SIGNIFICANT HOMOLOGY IN THE AMINO-TERMINUS

Hepatoma-derived growth actor (HDGF) is all acidic polypeptide with mi togenic activity for fibro-blasts performed outside the cells despite the presence of a putative nuclear localization signal (NLS). We have now cloned three related mouse cDNAs: one for a mouse homologue of hum an HDGF and two for additional HDGF-related proteins provisionally des ignated HDGF-related proteins 1 and 2 (HRP-1 and -2), Their deduced se quences have revealed that HDGF belongs to a new gene family with a hi ghly conserved 98-amino-acid sequence at the amino terminus (hath regi on, for homologous to the amino terminus of HDGF). HRP-1 and HRP-S pro teins are 46 and 432 amino acids longer than mouse HDGF, respectively, and have no conserved amino acid sequence other than the hath region. HRP-1 is a highly acidic protein (26% acidic) and also has a putative NLS. HRP-2 protein carries a mixed charge cluster, a sharp switch of positive-to negative-charge residues, which is often found in some nuc lear proteins. Northern blotting shows that mouse HDGF and HRP-2 are e xpressed predominantly in testis and skeletal muscle, to intermediate extents in heart, brain, lung, liver, and kidney, and to a minimal ext ent in spleen, HRP-1 is expressed specifically in testis. These findin gs suggest that the HDGF gene family might play a new role in the nucl eus especially in testis. (C) 1997 Academic Press.