A novel human gene similar to the protein kinase (PK) coding domain of thelarge subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) codes for a serine-threonine PK and is expressed in melanoma cells

The large subunit of herpes simplex virus type 2 ribonucleotide reductase ( ICP10) is a multifunctional protein that contains a serine-threonine protei n kinase (PK) activity (Nelson, J. W,, Zhu, J,, Smith, C. C,, Kulka, M., an d Aurelian, L. (1996) J, Biol. Chem. 271, 17021-17027). Phylogenetic analys es indicated that ICP10 PK belongs to a distinct subfamily of growth factor receptor serine-threonine PKs that are characterized by their ability to f unction with a limited number of conserved catalytic motifs (Hunter, J. C. R., Smith, C. C., and Aurelian, L. (1995) Int. J. One. 7, 515-522). Here, w e report the isolation and characterization of a novel gene, designated H11 , that contains an open reading frame of 588 nucleotides, which encodes a p rotein similar to ICP10 ph, The H11 protein has Mn2+-dependent serine-threo nine-specific PK activity as determined with a GST-H11 fusion protein and b y immunocomplex PK immunoblotting assays of 293 cells transfected with a H1 1 eukaryotic expression vector. PK activity is ablated by mutation of Lys(1 13) within the presumtive catalytic motif II (invariant Lys), 293 cells sta bly transfected with H11 acquire anchorage-independent growth. Endogenous H 11 RNA and the H11 phosphoprotein are expressed in melanoma cell lines and primary melanoma tissues at levels higher than in normal melanocytes and in benign nevi. Melanoma cell proliferation is inhibited by treatment with an tisense oligonucleotides that inhibit H11 translation, suggesting that H11 expression is associated with cell growth.