Rapamycin inhibits protein kinase C activity and stimulates Na+ transport in A6 cells
| Autor: | Michael D. Rokaw, Michael West, John P. Johnson |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Vasopressins
Sodium chemistry.chemical_element Biological Transport Active Endogeny Stimulation Polyenes Biochemistry Epithelium Tacrolimus Tacrolimus Binding Proteins Xenopus laevis Cytosol Immunophilins Animals Insulin Molecular Biology Protein kinase C Heat-Shock Proteins Protein Kinase C Sirolimus Chemistry fungi Cell Membrane Cell Biology Ligand (biochemistry) Molecular biology Cell biology Rats body regions DNA-Binding Proteins FKBP sense organs Carrier Proteins |
| Zdroj: | The Journal of biological chemistry. 271(50) |
| ISSN: | 0021-9258 |
| Popis: | Rapamycin and FK506 have unique cellular effects despite the fact that they bind to the same set of immunophilins, the FK506 binding proteins (FKBP). We have previously reported that rapamycin (RAP) stimulates sodium transport in A6 cells. FK506 did not stimulate sodium transport but did inhibit the stimulation seen in RAP-treated cells. Since FKBP12 has been shown to have sequence homology with an endogenous inhibitor of protein kinase C (PKC) and PKC inhibition has been shown to increase Na+ channel activity in A6 cells, studies to determine the effect of RAP on PKC activity and its relationship to sodium transport were performed. Here we report that RAP stimulates sodium transport, and the effect is not additive to that seen with a cell-permeant inhibitor of PKCalpha and -beta subtypes. RAP significantly inhibits endogenous PKC activity in A6 cells both in membrane and cytosolic preparations. There is a strong correlation between the degree of inhibition of PKC activity and the stimulation of sodium transport by RAP. RAP has no effect on Na+/K+-ATPase activity over this time course. Purified recombinant FKBP12 with or without FK506 has no effect on PKC activity when incubated with a rat brain-derived PKC preparation of known activity. By contrast, RAP plus FKBP12 significantly inhibits PKC activity. RAP plus FKBP12 inhibits the PKCalpha and not the -beta subtype. The results demonstrate inhibition of PKC activity by RAP and not FK506 through its binding to FKBP12. The inhibition of PKC activity by RAP stimulates sodium transport in A6. The results therefore imply the existence of an endogenous RAP-like ligand which when bound to FKBP12 could regulate Na+ channel activity through this mechanism. |
| Databáze: | OpenAIRE |
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