D103 - Lecture 18 - Signaling IV.docx

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Biological Sciences
Grant Mac Gregor

A. Effective way to shut off PKA signaling? a. Breakdown of cAMP B. Secondary Messenger a. GPCR --> heterotrimeric G protein --> activates Phospholipase C --> cleaved IP2 into IP3+DAG--> i. IP3 1. Opens IP3-gated Ca2+ channels on the Endoplasmic Reticulum a. Calcium activates PKC ii. DAG 1. Anchors PKC onto the cell membrane B. DAG keeps PKC anchored at the inside of the cell membrane C. 2nd messenger a. Not big proteins b. Must be rapidly generated and removed by the cell c. Small molecules d. Not about the increase in 2nd messenger, it's about the CHANGE e. Secondary messengers are found in discrete sub-cellular compartments f.Steady-state concentration B. Rate of diffusion for 2nd messengers varies a. Ca2+ is slow i. Tightly regualted ii. Many proteins that regulate Ca2+ concentration iii. Ca2+ stays in a localized area, Calbindin prevents Ca2+ from diffusing freely B. Targets for trimeric G-Proteins a. Adenylyl Cyclase b. Etc.. B. Phospholipase C a. Cleaves PIP2 into IP3 and DAG b. IP3 activates IP3-gated Ca2+ channel on endoplasmic reticulum c. DAG anchors PKC to cell membrane i. PKC phosphorylates effector proteins B. Phosphatidyl Inositol (PI) a. Glycerol + inositol + phosphate + 2 fatty acyl chains b. Phosphates are add to any of the positions on the inositol sugar c. DAG i. Glycerol + 2 fatty acid chains B. Different Phospholipases a. Cleaves the phospholipids at other positions to create other
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