LOK IS A NOVEL MOUSE STE20-LIKE PROTEIN-KINASE THAT IS EXPRESSED PREDOMINANTLY IN LYMPHOCYTES

We have identified a new gene, designated lok (lymphocyte-oriented kin ase), that encodes a 966-amino acid protein kinase whose catalytic dom ain at the N terminus shows homology to that of the STE20 family membe rs involved in mitogen-activated protein (MAP) kinase cascades, The no n-catalytic domain of LOK does not have any similarity to that of othe r known members of the family, There is a proline-rich motif with Src homology region 3 binding potential, followed by a long coiled-coil st ructure at the C terminus. LOK is expressed as a 130-kDa protein, whic h was detected predominantly in lymphoid organs such as spleen, thymus , and bone marrow, in contrast to other mammalian members of the STE20 family, LOK phosphorylated itself as well as substrates such as myeli n basic protein and histone IIA on serine and threonine residues but n ot on tyrosine residues, establishing LOK as a novel serine/threonine kinase, When coexpressed in COS7 cells with the known MAP kinase isofo rms (ERK, JNK, and p38), LOK activated none of them in contrast to PAK -and GCK-related kinases, These results suggest that LOK could be invo lved in a novel signaling pathway in lymphocytes, which is distinct fr om the known MAP kinase cascades.