Negative regulation of ligand-initiated Ca(2+) uptake by PKC-beta II in differentiated HL60 cells.
In phagocytic cells, fMet-Leu-Phe triggers phosphoinositide remodeling, activation of protein kinase C (PKC), release of intracellular Ca(2+) and uptake of extracellular Ca(2+). Uptake of extracellular Ca(2+) can be triggered by store-operated Ca(2+) channels (SOCC) and via a receptor-operated nonselective cation channel(s). In neutrophilic HL60 cells, the PKC activator phorbol myristate acetate (PMA) activates multiple PKC isotypes, PKC-alpha, PKC-beta, and PKC-delta, and inhibits ligand-initiated mobilization of intracellular Ca(2+) and uptake of extracellular Ca(2+). Therefore PKC is a negative regulator at several points in Ca(2+) mobilization. In contrast, selective depletion of PKC-beta in HL60 cells by an antisense strategy enhanced fMet-Leu-Phe-initiated Ca(2+) uptake but not mobilization of intracellular Ca(2+). Thapsigargin-induced Ca(2+) uptake through SOCC was not affected by PKC-beta II depletion. Thus PKC-beta II is a selective negative regulator of Ca(2+) uptake but not release of intracellular Ca(2+) stores. PKC-beta II inhibits a receptor-operated cation or Ca(2+) channel, thus inhibiting ligand-initiated Ca(2+) uptake.
Korchak
H M
HM
Department of Pediatrics, University of Pennsylvania School of Medicine, The Joseph Stokes Jr. Research Institute of the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. korchak@email.chop.edu
Corkey
B E
BE
Yaney
G C
GC
Kilpatrick
L E
LE
D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D003600:Cytosol / Q000378:metabolism; D018922:HL-60 Cells / Q000473:pathology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D007527:Isoenzymes; D008024:Ligands; D016376:Oligonucleotides, Antisense; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D002118:Calcium