THE HSV-2 LA-1 ONCOPROTEIN IS A MEMBER OF A NOVEL FAMILY OF SERINE THREONINE RECEPTOR KINASES

The large subunit of the herpes simplex virus type 2 ribonucleotide re ductase (RR) (ICP10) is a chimera consisting of a serine/threonine (Se r/Thr) protein kinase (PK) domain preceded by a transmembrane (TM) seg ment at the amino terminus (LA-I oncoprotein) and the RR domain at the carboxy terminus. Human cells transformed by the LA-I oncogene consti tutively express the oncoprotein on the cell surface and internalize i t by the endocytic pathway as determined by immunogold staining and el ectron microscopy. The TM segment of the oncoprotein is required for c ell surface localization, consistent with the interpretation that the oncoprotein is a growth factor receptor. Amino acid sequence alignment and comparative computer-assisted phylogenetic analyses of the LA-1 o ncoprotein indicate that it is a member of the superfamily of growth f actor receptor Ser/Thr kinases. However, many structural differences, including the presence of two SH3-binding motifs located within the PK catalytic domain suggest that the LA-I oncoprotein is a member of a n ovel subfamily.