Abstract
Platelet-derived growth factor (PDGF)-induced Ca2+ signaling mechanisms were examined in cultured rat glomerular mesangial cells. PDGF-BB stimulated the tyrosine phosphorylation of phospholipase C (PLC)-γ1, the formation of a PLC-γ1/PDGF-β receptor membrane complex, and the generation of intracellular inositol 1,4,5-trisphosphate (IP3). Preincubation with a tyrosine kinase inhibitor (genistein) abolished these PDGF-induced responses. Activation of 1-pS Ca2+ channels in cell-attached patches by intrapipette PDGF-BB was also abolished by tyrosine kinase inhibition. In the absence of PDGF-BB, channels were activated in cell-attached patches exposed to intrapipette thapsigargin (IP3-independent releaser of intracellular Ca2+ stores) and in excised inside-out patches exposed to increasing 'cytoplasmic' Ca2+ (10-8 to 10-6 M). In cell-attached patches, channel activation by PDGF-BB was abolished when extracellular Ca2+ was <1 mM. In glomerular mesangial cells 1) PDGF-BB stimulates tyrosine phosphorylation of PLC-γ1, PDGF-β receptor/PLC-γ1 membrane complex formation, IP3 production, and 1- pS Ca2+ channel activity; 2) all four PDGF-induced responses are abolished by tyrosine kinase inhibition; 3) PDGF receptor-operated Ca2+ channels are sensitive to both intra- and extracellular Ca2+.
Original language | English (US) |
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Pages (from-to) | F994-F1003 |
Journal | American Journal of Physiology |
Volume | 271 |
Issue number | 5 PART 2 |
State | Published - Dec 16 1996 |
Keywords
- calcium signaling
- D-myo- inositol 1,4,5-trisphosphate
- phosphorylation
- platelet-derived growth factor
- tyrosine kinase
ASJC Scopus subject areas
- Physiology (medical)