Modulation of Ca2+ mobilization by protein kinase C in the submandibular duct cell line A253.
The expression of protein kinase C (PKC) isoforms and the modulation of Ca2+ mobilization by PKC were investigated in the human submandibular duct cell line A253. Three new PKC (nPKC) isoforms (delta, epsilon, and theta) and one atypical PKC (aPKC) isoform (lambda) are expressed in this cell line. No classical PKC (cPKC) isoforms were present. The effects of the PKC activator phorbol 12-myristate-13-acetate (PMA) and of the PKC inhibitors calphostin C (CC) and bisindolymaleimide I (BSM) on inositol 1,4,5-trisphosphate (IP3) and Ca2+ responses to ATP and to thapsigargin (TG) were investigated. Pre-exposure to PMA inhibited IP3 formation, Ca2+ release and Ca2+ influx in response to ATP. Pre-exposure to CC or BSM slightly enhanced IP3 formation but inhibited the Ca2+ release and the Ca2+ influx induced by ATP. In contrast, pre-exposure to PMA did not modify the Ca2+ release induced by TG, but reduced the influx of Ca2+ seen in the presence of this Ca2+-ATPase inhibitor. These results suggest that PKC modulates elements of the IP3/Ca2+ signal transduction pathway in A253 cells by (1) inhibiting phosphatidylinositol turnover and altering the sensitivity of the Ca2+ channels to IP3, (2) altering the activity, the sensitivity to inhibitors, or the distribution of the TG-sensitive Ca2+ ATPase, and (3) modulating Ca2+ entry pathways.
Sugita
K
K
Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284-7827, USA.
Mörk
A C
AC
Zhang
G H
GH
Martinez
J R
JR
D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018987:Salivary Ducts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction; D013363:Submandibular Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D007527:Isoenzymes; D010716:Phosphatidylinositols; D019284:Thapsigargin; D011493:Protein Kinase C; D002118:Calcium