Use of an alternate splice donor site in the human GAP gene is responsible for synthesis of the p100 isoform |
| |
| Institution: | 1. Department of Science and Education, Second People''s Hospital of Nantong, Nantong University, Nantong, Jiangsu Province 226001, China;2. Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China;3. Department of Histology and Embryology, Medical College, Nantong University, Nantong, Jiangsu 226001, China;4. Department of Neurology, Nantong University Affiliated Mental Health Center, Nantong, Jiangsu 226001, China;5. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong, Jiangsu Province 226001, China;6. Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China;7. Department of Genetics, Genomics and Informatics, USA;8. Anatomy and Neurobiology, University of Tennessee Health Science Center, USA;1. Division of Cardiology, Rocky Mountain Regional VA Medical Center, University of Colorado, Denver, CO, USA;2. Cardiovascular Systems, Inc., St. Paul, MN, USA;1. Division of Cardiovascular Medicine, Henry Ford Health System, Detroit, MI;2. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI;3. Department of Medicine, Section of Cardiology, Veterans Affairs Medical Center, Ann Arbor, MI;4. Wayne State University, School of Medicine, Detroit, MI |
| |
| Abstract: | GAP (GTPase-activating protein), a negative regulator of the receptor tyrosine kinase signal transduction pathway, exists as two isoforms: a ubiquitous, p120 form and a primate placenta-specific p100 form lacking the N-terminal hydrophobic domain. The cDNA species encoding p120 and p100 GAP are identical except that p100 GAP cDNA contains a 65-bp insert not present in p120 cDNA. The purpose of this study was to locate the 65-bp insert in the genomic GAP sequence, thereby determining the mechanism by which alternate splicing produces the two mRNA species. It was found that the 65-bp insert is located just 3′ to the sequence encoding the hydrophobic domain, indicating that the p100 form of GAP results from utilization of an alternate splice donor site. In addition, the sequence encoding the hydrophobic domain was found to be contained within a single large exon. The intron separating this exon from the exon encoding the 5′-portion of the SH2-N domain was determined to be at least 40 kb in length. Finally, it was found that the sequence encoding the SH2-N domain contains an intron 1006 bp long, and the sequence of this intron has been deduced. It is anticipated that the data presented in this paper will provide the basis for elucidating RNA processing mechanisms responsible for preferential expression of p100 GAP in the human placenta. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
