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Corticotropin-Releasing Factor Increases Protein Kinase C Activity by Elevating Membrane-Bound αandβ Isoforms

並列摘要


Corticotropin-releasing factor (CRF) has been shown to attenuate vascular leakage in injured skin, mucous membrane, muscle, lung, and brain. We previously reported that CRF increases cytosolic free calcium concentrations ([Ca(superscript 2+)]i), cellular cAMP, and inositol trisphosphates in human epidermoid A-431 cells. This study identified protein kinase C isoforms in A.431 cells and investigated the effect of CRF on PKC activity and isoform translocation. PKC α,β, γ,δ, and ζisoforms were present in cytosolic and membrane fractions, but the ε isoform was detected only in the membrane fraction. Exposure of cells to CRF at 420 pM for 1 mm increased PKC activity and led to the translocation of PKC A and fi isoforms from cytosol to membrane. The translocation was dependent on an increase in ([Ca(superscript 2+)]i), because cells treated with 100μM BAPTA-am (an intracellular Ca(superscript 2+) chelator), then exposed to CRF, showed neither increases in PKC activity nor translocation of PKC isoforms. This suggests that a CRF. induced increase in [Ca(superscript 2+)]i)1 mediates the increase in PKC activity.

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