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Lipid Signaling in Cells Focus on Phospholipase C and Protein Kinase C Terry B. Rogers Department of Biochemistry & Molecular Biology Rm. 215, 108 N. Greene Street Tel 410.706.3169 Email: trogers@som.umaryland.edu. PLC. O-FA. AA-O. OH. 1,2 Diacyglycerol. +. POX.
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Lipid Signaling in CellsFocus on Phospholipase C and Protein Kinase CTerry B. RogersDepartment of Biochemistry & Molecular BiologyRm. 215, 108 N. Greene StreetTel 410.706.3169Email: trogers@som.umaryland.edu
PLC O-FA AA-O OH 1,2 Diacyglycerol + POX Major Families of Phospholipid Phospholipases O-FA AA-O O-P- OX PLA2 PLD O-FA O-FA AA-O HO O-POX O-PO3 Lysophospholipid Phosphatidic Acid + + Arachidonic Acid HO-X
Prostaglandins Thromboxanes Cycloxygenases Arachidonic Acid Lipoxygenases Leukotrienes HETEs
The phospholipase C –DAG Protein kinase C signaling cascade
Reaction catalyzed by Phosphoinositide-specific phospholipase C O-FA O-FA + Ins(1,4,5)P3 O-AA O-AA O-P-Ins(4,5)P2 O-H IP3 1,2 DAG PIP2
Gq Phospholipase C – IP3/Protein kinase C Signaling Pathway AngIIET1Phe Diacylglycerol Phospholipase C Protein Kinase C IP3 Ca2+
Gq Phospholipase C – IP3/Protein kinase C Signaling Pathway AngIIET1Phe [3H]inositol Diacylglycerol InsP2 Phospholipase C InsP3 + [32P]ATP DAG Kinase PO4
InaD protein functions as a scaffold organizing many signaling Proteins in coordinated complex
Activated by an atypical GTP binding protein, Gh Ca also activates this species in 1 M
The phospholipase C –DAG Protein kinase C signaling cascade
In NG108-15 cells PKC isoform is seen in the Golgi in control conditions and translocates to nucleus and perinuclear regions following stimulation Clearly simple DAG activation model is not sufficient to explain PKC cell biology
AKAPS can function as signalling scaffold -- organizing multiple kinases and phosphatases into one module
RACKS – receptors for activated Ckinases Peptides derived from RACK binding motif will block PKC trans- location and function