Molecular Biochemistry I

Signal Transduction Cascades

Reading:

Textbook Reading: Biochemistry, 3rd Edition, by Voet & Voet, pages 673-683, 707-717. (Note: Not all details in these pages will be covered here.)

Some recent articles (optional reading): 
M. B. Yaffe & S. J. Smerdon (2004) "The use of in vitro peptide-library screens in the analysis of phosphoserine/threonine-binding domain structure and function," Annu. Rev. Biophys. Biomol. Struct. 33: 225-244.
G. Li & X. C. Zhang (2004) "GTP hydrolysis mechanism of Ras-like GTPases," J. Mol. Biol. 340: 921-932.
D. P. Brazil, Z. Z. Yang & B. A. Hemmings (2004) "Advances in protein kinase B signalling: AKTion on multiple fronts," Trends in Biochem. Sci. 29: 233-242.
K. Pattni & G. Banting (2004) "Ins(1,4,5)P3 metabolism and the family of IP3-3 Kinases," Cellular Signalling 16: 643-654.
S. M. Lanier (2004) "AGS proteins, GPR motifs and the signals processed by heterotrimeric G proteins," Biol. of the Cell 96: 369-372.
C. C. Malbon, J. Tao & H.-Y. Wang (2004) "AKAPs (A-kinase anchoring proteins) and molecules that compose their G-protein-coupled receptor signalling complexes," Biochem. J. 379: 1-9.
R. J. Lefkowitz & S. K. Shenoy (2005) "Transduction of receptor signals by b-arrestins," Science 308: 512-517.
J. Bockaert, G. Roussignol, C. Becamel, S. Gavarini, L. Joubert, A. Dumuis, L. Fagni & P. Marin (2004) "GPCR-interacting proteins (GIPs): nature and functions," Biochem. Soc. Trans. 32: 851-855.
L. F. Agnati, K. Fuxe & S. Ferr (2005) "How receptor mosaics decode transmitter signals. Possible relevance of cooperativity," Trends in Biochem. Sci. 30: 188-193.
B. N. Armbruster & B. L. Roth (2005) "Mining the receptorome," J. Biol. Chem. 280: 5129-5132.
R. Maggio, F. Novi, M. Scarselli & G. U. Corsini (2005) "The impact of G-protein-coupled receptor hetero-oligomerization on function and pharmacology," FEBS J. 272: 2939-2946.
F. D. Smith, L. K. Langeberg & J. D. Scott (2006) "The where's and when's of kinase anchoring," Trends in Biochem. Sci. 31: 316-323.
F. D. Smith & J. D. Scott (2006) "Anchored cAMP signaling: Onward and upward - A short history of compartmentalized cAMP signal transduction," Eur. J. Cell Biol. 85: 585-592.
A. Aitken (2006) "14-3-3 proteins: A historic overview," Seminars in Cancer Biol. 16: 162-172.
L. Birnbaumer (2007) "Expansion of signal transduction by G proteins. The second 15 years or so: From 3 to 16 a subunits plus bg dimers," Biochim. Biophys. Acta 1768: 772-793.
P. L. Yeagle & A. D. Albert (2007) "G-protein coupled receptor structure," Biochim. Biophys. Acta 1768: 808-824.
B. K. Kobilka (2007) "G protein coupled receptor structure and activation," Biochim. Biophys. Acta 1768: 794-807.
E. F. Grady (2007) "b-Arrestin, a two-fisted terminator," Science 315: 605-606.
V. Cherezov, D. M. Rosenbaum, M. A. Hanson, S. G. F. Rasmussen, F. S. Thian, T. S. Kobilka, H.-J. Choi, P. Kuhn, W. I. Weis, B. K. Kobilka & R. C. Stevens (2007) "High-resolution crystal structure of an engineered human b2-adrenergic G protein-coupled receptor," Science 318: 1258-1265.

Potential Test Questions:

1. Diagram and describe the sequence of events by which a hormone such as epinephrine or glucagon activates production of cyclic AMP within a cell. Include the roles of the receptor (GPCR), the different subunits of the stimulatory G protein, and Adenylate Cyclase. How is the signal turned off at each step? Include a brief description of the role b-arrestin.

2. a. Describe the activation of cAMP-Dependent Protein Kinase (Protein Kinase A). What causes the enzyme to be inhibited in the absence of cyclic AMP? How is activation by cyclic AMP turned off?
b. Diagram an example of the reaction catalyzed by the activated cAMP-Dependent Protein Kinase. What reaction is catalyzed by the enzyme Protein Phosphatase.
c. Briefly summarize the role of an AKAP.

3. Write out (in words) the reaction catalyzed by Phospholipase C. Briefly summarize the "second messenger" roles of the two products of the Phospholipase C reaction.

Copyright 1998-2008 by Joyce J. Diwan. All rights reserved.

Lecture notes on
Signal Transduction Cascades  

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Signal Transduction   

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