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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shively, John E. Nguyen, Tung Chen, Charng-jui |
| Description | Author Affiliation: Nguyen T ( From the Department of Immunology, Beckman Research Institute of City of Hope, Duarte, California 91010.) |
| Abstract | Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), a transmembrane protein, expressed on normal breast epithelial cells is down-regulated in breast cancer. Phosphorylation of Thr-457 on the short cytoplasmic domain isoform (CEACAM1-SF) that is predominant in normal epithelial cells is required for lumen formation in a three-dimensional model that involves apoptosis of the central acinar cells. Calmodulin kinase IID (CaMKIID) was selected as a candidate for the kinase required for Thr-457 phosphorylation from a gene chip analysis comparing genes up-regulated in MCF7 cells expressing wild type CEACAM1-SF compared with the T457A-mutated gene (Chen, C. J., Kirshner, J., Sherman, M. A., Hu, W., Nguyen, T., and Shively, J. E. (2007) J. Biol. Chem. 282, 5749-5760). Up-regulation of CaMKIID during lumen formation was confirmed by analysis of mRNA and protein levels. CaMKIID was able to phosphorylate a synthetic peptide corresponding to the cytoplasmic domain of CEACAM1-SF and was covalently bound to biotinylated and T457C-modified peptide in the presence of a kinase trap previously described by Shokat and co-workers (Maly, D. J., Allen, J. A., and Shokat, K. M. (2004) J. Am. Chem. Soc. 126, 9160-9161). When cell lysates from wild type-transfected MCF7 cells undergoing lumen formation were incubated with the peptide and kinase trap, a cross-linked band corresponding to CaMKIID was observed. When these cells were treated with an RNAi that inhibits CaMKIID expression, lumen formation was blocked by over 90%. We conclude that CaMKIID specifically phosphorylates Thr-457 on CEACAM1-SF, which in turn regulates the process of lumen formation via apoptosis of the central acinar cells. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 5 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-01-31 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD Metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2 Cell Adhesion Molecules Epithelial Cells Cytology Mammary Glands, Human Adenocarcinoma Pathology Amino Acid Sequence Genetics Apoptosis Physiology Benzylamines Pharmacology Breast Neoplasms Cell Culture Techniques MCF-7 Cells Anatomy & Histology Molecular Sequence Data Mutagenesis Oligonucleotide Array Sequence Analysis Phosphorylation Protein Kinase Inhibitors RNA, Small Interfering Sulfonamides Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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