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 chromosome 11q13 region. Comparisons of the EMS1 sequences with those present in the GenBank databases revealed a high identity with chicken cortactin. Southern and western blot analyses confirm the high sequence conservation during evolution. An antiserum specific for human cortactin, showed in gene transfer experiments that both human p80 and p85 isoforms are encoded by the EMS1 cDNA. Further comparisons demonstrated an high sequence and structural homology with HS1 that is implicated in signal transduction in lymphoid cells only. Expression of EMS1/cortactin mRNA was restricted to tumor cell lines derived from non-lymphoid origin. Cortactin contains (i) a filamentous actin binding tandem repeat domain, (ii) a proline-rich SH3-binding and (iii) a SH3 domain that is common in proteins involved in signal transduction. Our data suggest that human EMS1/cortactin has a function in signal transmission between cell-matrix contact sites and the cytoskeleton and, as such, its overexpression due to 11q13 amplification might effect adhesive properties of human carcinomas.
Schuuring
E
E
Department of Pathology, Leiden University Medical Center, The Netherlands. e.m.d.schuuring@pathology.medfac.leidenuniv.nl
van Damme
H
H
Schuuring-Scholtes
E
E
Verhoeven
E
E
Michalides
R
R
Geelen
E
E
de Boer
C
C
Brok
H
H
van Buuren
V
V
Kluin
P
P
D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D002448:Cell Adhesion / Q000502:physiology; D002880:Chromosomes, Human, Pair 11; D051356:Cortactin; D019938:Cyclin D1 / Q000502:physiology; D019143:Evolution, Molecular; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000502:physiology
D000906:Antibodies; C495868:CTTN protein, human; D051356:Cortactin; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019938:Cyclin D1