Negative regulation of ligand-initiated Ca2+uptake by PKC-βII in differentiated HL60 cells

Helen M. Korchak, Barbara E. Corkey, Gordon C. Yaney, Laurie E. Kilpatrick
2001 American Journal of Physiology - Cell Physiology  
Negative regulation of ligand-initiated Ca 2ϩ uptake by PKC-␤II in differentiated HL60 cells. Am J Physiol Cell Physiol 281: C514-C523, 2001.-In phagocytic cells, fMet-Leu-Phe triggers phosphoinositide remodeling, activation of protein kinase C (PKC), release of intracellular Ca 2ϩ and uptake of extracellular Ca 2ϩ . Uptake of extracellular Ca 2ϩ can be triggered by storeoperated Ca 2ϩ channels (SOCC) and via a receptor-operated nonselective cation channel(s). In neutrophilic HL60 cells, the
more » ... HL60 cells, the PKC activator phorbol myristate acetate (PMA) activates multiple PKC isotypes, PKC-␣, PKC-␤, and PKC-␦, and inhibits ligand-initiated mobilization of intracellular Ca 2ϩ and uptake of extracellular Ca 2ϩ . Therefore PKC is a negative regulator at several points in Ca 2ϩ mobilization. In contrast, selective depletion of PKC-␤ in HL60 cells by an antisense strategy enhanced fMet-Leu-Phe-initiated Ca 2ϩ uptake but not mobilization of intracellular Ca 2ϩ . Thapsigargin-induced Ca 2ϩ uptake through SOCC was not affected by PKC-␤II depletion. Thus PKC-␤II is a selective negative regulator of Ca 2ϩ uptake but not release of intracellular Ca 2ϩ stores. PKC-␤II inhibits a receptor-operated cation or Ca 2ϩ channel, thus inhibiting ligand-initiated Ca 2ϩ uptake. calcium mobilization; protein kinase C isotypes; inositol 1,4,5-trisphosphate; signal transduction Address for reprint requests and other correspondence: H. M.
doi:10.1152/ajpcell.2001.281.2.c514 pmid:11443050 fatcat:rglqvvqg4baitfc5hy7srp2zze