The large subunit of the herpes simplex virus type 2 ribonucleotide reductase (RR) (ICP10) is a chimera consisting of a serine/threonine (Ser/Thr) protein kinase (PK) domain preceded by a transmembrane (TM) segment at the amino terminus (LA-I oncoprotein) and the RR domain at the carboxy terminus. Human cells transformed by the LA-I oncogene constitutively express the oncoprotein on the cell surface and internalize it by the endocytic pathway as determined by immunogold staining and electron microscopy. The TM segment of the oncoprotein is required for cell 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 oncoprotein indicate that it is a member of the superfamily of growth factor 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 novel subfamily.

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