FINE MAPPING OF THE MLK-3 GENE WITHIN 11Q13 AND ITS EXCLUSION AS THE MEN1 SUSCEPTIBILITY GENE

MLK-3 kinase is a widely expressed serine/threonine kinase that bears multiple protein interaction domains and regulates signals mediated by the stress-responsive pathway. Thus, MLK-3 signaling affects numerous cellular processes, raising the possibility that MLK-3 might play a r ole in oncogenesis. In this report, we describe the fine mapping of th e MLK-3 gene within the 11q13.1 chromosomal region. By integrating dat a from somatic cell hybrids and double color fluorescence in situ hybr idization on metaphase chromosomes and DNA fibers, MLK-3 has been assi gned approximately 1 Mb telomeric of PYGM, close to the D11S546 locus. Since the MEN1 susceptibility locus is also located within the 11q13. 1 region, we have carried out Southern and Northern blot analyses, as well as protein truncation assays to establish whether abnormalities i n MLK-3 lead to the development of this familial cancer syndrome. Our observations exclude MLK-3 as the MEN1 gene.