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O-FA PowerPoint Presentation

O-FA

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O-FA

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  1. 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

  2. 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

  3. Prostaglandins Thromboxanes Cycloxygenases Arachidonic Acid Lipoxygenases Leukotrienes HETEs

  4. The phospholipase C –DAG Protein kinase C signaling cascade

  5. 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

  6. Basic structure of the multidomain PLC proteins

  7. Gq Phospholipase C – IP3/Protein kinase C Signaling Pathway AngIIET1Phe Diacylglycerol Phospholipase C Protein Kinase C IP3 Ca2+

  8. Gq Phospholipase C – IP3/Protein kinase C Signaling Pathway AngIIET1Phe [3H]inositol Diacylglycerol InsP2 Phospholipase C InsP3 + [32P]ATP DAG Kinase PO4

  9. Structural Motif of PLB Family `

  10. InaD protein functions as a scaffold organizing many signaling Proteins in coordinated complex

  11. Structure of PLC- Family

  12. Mechanism of activation of PLC1

  13. Activated by an atypical GTP binding protein, Gh Ca also activates this species in 1 M

  14. Hierarchy of PLC subtypes in cell signaling

  15. Protein Kinase C

  16. The phospholipase C –DAG Protein kinase C signaling cascade

  17. 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

  18. DAG site

  19. AKAPS can function as signalling scaffold -- organizing multiple kinases and phosphatases into one module

  20. RACKS – receptors for activated Ckinases Peptides derived from RACK binding motif will block PKC trans- location and function