MLK-3 - IDENTIFICATION OF A WIDELY-EXPRESSED PROTEIN-KINASE BEARING AN SH3 DOMAIN AND A LEUCINE ZIPPER-BASIC REGION DOMAIN

We have identified a novel protein kinase, designated MLK-3, from huma n thymus using RT-PCR and cDNA library screening. The deduced open rea ding frame, derived from sequencing a 3.5 kb MLK-3 cDNA, encodes a pro tein of 847 amino acids with several interesting structural features. These include an SH3 domain in the absence of an SH2 domain, a region containing two leucine zippers with an adjacent carboxy-terminal basic region, and a proline rich region. This kinase shows homology with th e mixed-lineage family of protein kinases (MLK) and shares the unusual leucine zipper-basic motif found in previously identified MLK kinases . By northern analysis, MLK-3 mRNA was detected in a wide variety of n ormal and transformed human cell lines and tissue specimens. The gene encoding MLK-3 has been mapped using fluorescence in situ hybridizatio n to human chromosome 11 q13.1-13.3, a region frequently altered in hu man malignancies.