Mechanism of activation of protein kinase D2(PKD2) by the CCK(B)/gastrin receptor
| Autor: | Annette Gilchrist, Jackie R. Vandenheede, Johan Van Lint, Guido Adler, Sabine Sturany, Thomas Seufferlein |
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| Rok vydání: | 2002 |
| Předmět: |
urologic and male genital diseases
Biochemistry Cell Line Heterotrimeric G protein Gastrins Humans Phosphorylation Protein kinase A Molecular Biology Protein kinase C Diacylglycerol kinase Gastrin biology Phospholipase C urogenital system digestive oral and skin physiology Cell Biology Molecular biology Heterotrimeric GTP-Binding Proteins female genital diseases and pregnancy complications Enzyme Activation Gq alpha subunit Type C Phospholipases biology.protein Receptors Cholecystokinin Signal transduction Protein Kinases hormones hormone substitutes and hormone antagonists Protein Kinase D2 Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 277(33) |
| ISSN: | 0021-9258 |
| Popis: | Recently, we cloned a novel serine/threonine kinase termed protein kinase D2 (PKD2). PKD2 can be activated by phorbol esters both in vivo and in vitro but also by gastrin via the cholecystokinin/CCK(B) receptor in human gastric cancer cells stably transfected with the CCK(B)/gastrin receptor (AGS-B cells). Here we identify the mechanisms of gastrin-induced PKD2 activation in AGS-B cells. PKD2 phosphorylation in response to gastrin was rapid, reaching a maximum after 10 min of incubation. Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta. These PKCs are activated by gastrin in AGS-B cells. Thus, PKD2 is likely to be a novel downstream target of specific PKCs upon the stimulation of AGS-B cells with gastrin. Our data suggest a two-step mechanism of activation of PKD2 via endogenously produced diacylglycerol and the activation of PKCs. |
| Databáze: | OpenAIRE |
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