Chapter 14: Signal Transduction

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Presentation transcript:

Chapter 14: Signal Transduction

Examples of Common Cellular Signals

Common 2o Messengers

Functions of 7TM 7TM receptors are the root of 4 of the 5 senses in the human body. Nearly, 1/3 of all drugs target these receptors. More than 20,000 receptors are known.

G-Protein and 2012 Nobel Prize 7TM Receptor “The Nobel Prize in Chemistry for 2012 has been awarded to Robert Lefkowitz (left), Howard Hughes Medical Institute, Duke University, USA, and Brian Kobilka (right), Stanford University, USA, for their work on G-protein-coupled receptors (GPCRs).” G-Protein - Chemistry Views 2012

The Overall 7TM -> G-Protein -> Adenylate cyclase Process Activation: Deactivation:

G-Protein Activation of Phospholipase C G-Protein (Gq) activated, which then activates Phopholipase C (PLC). PLC job is to cleave Inositol 1,4,5-triphosphate (IP3) from PIP2 a fatty acid in the membrane (shown above)

Overall Process Results of Ca2+ release: Activation of Diacylglycerol (DAG) which activate Protein kinase C (which then phosphorylates and activates/deactivates various proteins) Ca2+ itself also binds to calmodulin among other proteins to trigger smooth muscle contraction, glycogen breakdown, and vesicle release.

Conformation Changes in a Tyrosine Kinase Phosphorylated Tyrosines exposed!

How could some Proteins be attracted to the Phosphorylated Tyrosine Receptor? Answer: Phosphate is Negatively charged, therefore it will attract positively charged Amino Acids (Lys and Arg) of proteins and can form strong salt bridges. Keep in mind that the protein being attracted still must have the perfect 3D shape to interact well with the Tyrosine Receptor. The example of the SH2 domain (left) does this.

A Look into the Insulin Receptor Pathway

EGF dimerization arms

EGF Mechanism