Ogunwobi Olorunseun O, Beales Ian L P
Biomedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, United Kingdom.
Mol Cell Endocrinol. 2008 Dec 16;296(1-2):94-102. doi: 10.1016/j.mce.2008.08.004. Epub 2008 Aug 15.
Glycine-extended gastrin (G-Gly) is a mitogen for several gastrointestinal tissues although the mechanisms responsible are ill-defined and it is unknown if G-Gly can influence signalling in Barrett's oesophagus. G-Gly stimulated proliferation in OE19 and OE33 cells in a dose-dependant manner. This was unaffected by a CCK2 receptor antagonist but abolished by COX-2 inhibitors. G-Gly induced proliferation, COX-2 mRNA abundance, and PGE2 secretion, were all abolished by inhibition of JAK2, PI3-kinase, Akt or NF-kappaB. G-Gly stimulated phosphorylation of JAK2 and increased PI3-kinase activity in JAK2 immunoprecipitates. G-Gly increased Akt phosphorylation and kinase activity and NF-kappaB reporter activity in a JAK2-, PI3-kinase- and Akt-sensitive manner. G-Gly increased COX-2 promoter transcription in an Akt and NF-kappaB-dependent manner and also reduced COX-2 mRNA degradation in an Akt-insensitive manner. We conclude that G-Gly induced signalling involves a JAK2/PI3-kinase/Akt/NF-kappaB sequence leading to COX-2 transcription. G-Gly also seems to stabilise COX-2 mRNA via a separate pathway.
甘氨酸延伸胃泌素（G-Gly）是几种胃肠道组织的促有丝分裂原，尽管其作用机制尚不明确，并且G-Gly是否能影响巴雷特食管中的信号传导也不清楚。G-Gly以剂量依赖的方式刺激OE19和OE33细胞的增殖。这不受CCK2受体拮抗剂的影响，但被COX-2抑制剂所消除。G-Gly诱导的增殖、COX-2 mRNA丰度和PGE2分泌，在抑制JAK2、PI3激酶、Akt或NF-κB后均被消除。G-Gly刺激JAK2的磷酸化并增加JAK2免疫沉淀物中的PI3激酶活性。G-Gly以JAK2、PI3激酶和Akt敏感的方式增加Akt磷酸化和激酶活性以及NF-κB报告基因活性。G-Gly以Akt和NF-κB依赖的方式增加COX-2启动子转录，并且还以Akt不敏感的方式减少COX-2 mRNA降解。我们得出结论，G-Gly诱导的信号传导涉及JAK2/PI3激酶/Akt/NF-κB序列，导致COX-2转录。G-Gly似乎还通过一条独立的途径稳定COX-2 mRNA。
