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The annexin 2-S100A10 complex and its association with TRPV6 is regulated by cAMP/PKA/CnA in airway and gut epithelia Borthwick LA; Neal A; Hobson L; Gerke V; Robson L; Muimo RCell Calcium 2008[Aug]; 44 (2): 147-57The formation of a heterotetrameric complex between annexin 2 (anx 2) and S100A10 plays an important role in regulating the cellular distribution and biochemical properties of anx 2. A major distinction between the anx 2-S100A10 complex and other annexin-S100 complexes is that S100A10 binding to anx 2 occurs independently of calcium. Here we describe a cyclic 3',5'-adenosine monophosphate (cAMP) and cAMP-dependent protein kinase (PKA, EC 2.7.1.37)-dependent mechanism regulating anx 2-S100A10 complex formation and its interaction with the transient receptor potential vanilloid type 6 channel (TRPV6) in airway and gut epithelia. In both 16HBE14o- and Caco-2 cells, forskolin (FSK) stimulated increased anx 2-S100A10 complex formation, which was attenuated by either PKA inhibitors or calcineurin A (CnA) inhibitors. The anx 2-S100A10 complex association with TRPV6 was dependent on FSK-induced CnA-dependent dephosphorylation of anx 2. Analysis of the significance of the cAMP/PKA/CnA pathway on calcium influx showed that both PKA and CnA inhibitors attenuated Ca(45) uptake in Caco-2, but not 16HBE14o-, cells. Thus, the cAMP/PKA/CnA-induced anx 2-S100A10/TRPV6 complex may require additional factors for calcium influx or play a role independent of calcium influx in airway epithelia. In conclusion, our data demonstrates that cAMP/PKA/CnA signalling is important for anx 2-S100A10 complex formation and interaction with target molecules in both absorptive and secretory epithelia.|Annexin A2/*metabolism[MESH]|Blotting, Western[MESH]|Caco-2 Cells[MESH]|Calcineurin/*physiology[MESH]|Calcium Channels/*metabolism[MESH]|Calcium/metabolism[MESH]|Cell Membrane/metabolism[MESH]|Cyclic AMP-Dependent Protein Kinases/*physiology[MESH]|Cyclic AMP/*physiology[MESH]|Cytosol/metabolism[MESH]|Epithelium/metabolism[MESH]|Humans[MESH]|Immunoprecipitation[MESH]|Intestinal Mucosa/cytology/metabolism[MESH]|Respiratory Mucosa[MESH]|Respiratory System/cytology/*metabolism[MESH]|S100 Proteins/*metabolism[MESH]|Signal Transduction/physiology[MESH]|TRPV Cation Channels/*metabolism[MESH] |
