Cellular calcium mobilization in response to phosphoinositide delivery.
Intracellular calcium [Ca(2+)](i) is mobilized in many cell types in response to activation of phosphoinositide (PIP(n)) signaling pathways involving PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3). To further explore the relationship between increases in intracellular PIP(n) concentrations and mobilization of [Ca(2+)](i), each of the seven phosphorylated phosphoinositides (PIP(n)s) were delivered into cells and the metabolism and physiological effects of the exogenously administered PIP(n)s were determined. The efficient cellular delivery of fluorophore-tagged and native PIP(n)s was accomplished using histone protein, neomycin, and dendrimeric polyamines. PtdIns(4,5)P(2) fluorophore-tagged analogs with short- and long-acyl chains were substrates for cellular enzymes in vitro and for phospholipases in stimulated fibroblasts. PtdIns(4)P, PtdIns(3,4)P(2) and PtdIns(4,5)P(2), each induced calcium mobilization rapidly after exogenous addition to fibroblasts. PtdIns(3,4,5)P(3) induced a significant, but smaller increase in intracellular calcium. These observations suggest that PIP(n)s other than PtdIns(4,5)P(2) or PtdIns(3,4,5)P(3) may have direct roles in signaling involving [Ca(2+)](i).
Dewald
Daryll B
DB
Department of Biology, Utah State University, Logan, 84322-5305, USA. dewald@biology.usu.edu
Ozaki
Shoichiro
S
Malaviya
Swati
S
Shope
Joseph C
JC
Manabe
Kelly
K
Crosby
Lee
L
Neilsen
Paul
P
Johnston
Derrick
D
Harihar
Sitaram
S
Prestwich
Glenn D
GD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005456:Fluorescent Dyes; D006657:Histones / Q000378:metabolism / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D010716:Phosphatidylinositols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D005456:Fluorescent Dyes; D006657:Histones; D046911:Macromolecular Substances; D010716:Phosphatidylinositols; D002118:Calcium