CHARACTERIZATION OF THE EMS1 GENE AND ITS PRODUCT, HUMAN CORTACTIN

We have identified a novel gene, EMS1, that is consistently amplified and overexpressed in human carcinomas with an amplification of the chr omosome 11q13 region. Comparisons of the EMS1 sequences with those pre sent in the GenBank databases revealed a high identity with chicken co rtactin. Southern and western blot analyses confirm the high sequence conservation during evolution. An antiserum specific for human cortact in, showed in gene transfer experiments that both human p80 and p85 is oforms are encoded by the EMS1 cDNA. Further comparisons demonstrated an high sequence and structural homology with HS1 that is implicated i n signal transduction in lymphoid cells only. Expression of EMS1/corta ctin mRNA was restricted to tumor cell lines derived from non-lymphoid origin. Cortactin contains (i) a filamentous actin binding tandem rep eat domain, (ii) a proline-rich SH3-binding and (iii) a SH3 domain tha t is common in proteins involved in signal transduction. Our data sugg est that human EMS1/cortactin has a function in signal transmission be tween cell-matrix contact sites and the cytoskeleton and, as such, its overexpression due to 11q13 amplification might effect adhesive prope rties of human carcinomas.