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Glucagon Signal‐Transduction Mechanisms

J. H. Exton

10.1002/cphy.cp070213

Source: Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Glucagon Receptor
2 Regulation of Gs
3 Regulation of Adenylate Cyclase
4 Regulation of cAmp‐Dependent Protein Kinase
5 Substrates of cAmp‐Dependent Protein Kinase
6 Mechanisms of Calcium Mobilization Induced by Glucagon
7 Summary
Figure 1. Figure 1.

Putative structure of glucagon receptor, showing the extracellular N‐terminal tail, the intracellular C‐terminal tail, and the seven transmembrane domains (I‐VII).
Figure 2. Figure 2.

Operating scheme for heterotrimeric G proteins. In the resting state, the G protein consists of associated α, β, and γ subunits. Activation of the receptor by agonist leads to promotion of GTP‐GDP exchange on the α subunit. The GTP‐liganded α subunit then dissociates from the αγ complex. The free subunits then interact with effector proteins for example, adenylyate cyclase, to control their activity. Due to the intrinsic GTPase of the α subunit, GTP is hydrolyzed to GDP and the GDP‐liganded α subunit reassociates with the βγ complex to reform the heterotrimeric G protein. In the continued presence of agonist and active receptor, the cycle is repeated and the changes in effector activity are maintained. Pi, inorganic phosphate.
Figure 3. Figure 3.

Schematic representation of the structure of adenylate cyclase. Cylinders represent membrane‐spanning regions, and M1 and M2 are the first and second sets of these regions, respectively. C1a and C1b represent the first large cytoplasmic domain and C2a and C2b the second such intracellular domain. Bold sections indicate regions of high sequence homology among different cyclases. The N terminus (N) and a glycosylation site are also shown.
Figure 4. Figure 4.

Putative structure of cAMP‐dependent protein kinase, showing a regulatory subunit dimer and two catalytic subunits. The regulatory subunits show the two separate cAMP‐bindings sites (A and B), the autoinhibitory domain (including the autophosphorylation site for the type II enzyme), and the dimerization domain. The catalytic subunits show the binding sites for ATP and protein substrate.


Figure 1.

Putative structure of glucagon receptor, showing the extracellular N‐terminal tail, the intracellular C‐terminal tail, and the seven transmembrane domains (I‐VII).



Figure 2.

Operating scheme for heterotrimeric G proteins. In the resting state, the G protein consists of associated α, β, and γ subunits. Activation of the receptor by agonist leads to promotion of GTP‐GDP exchange on the α subunit. The GTP‐liganded α subunit then dissociates from the αγ complex. The free subunits then interact with effector proteins for example, adenylyate cyclase, to control their activity. Due to the intrinsic GTPase of the α subunit, GTP is hydrolyzed to GDP and the GDP‐liganded α subunit reassociates with the βγ complex to reform the heterotrimeric G protein. In the continued presence of agonist and active receptor, the cycle is repeated and the changes in effector activity are maintained. Pi, inorganic phosphate.



Figure 3.

Schematic representation of the structure of adenylate cyclase. Cylinders represent membrane‐spanning regions, and M1 and M2 are the first and second sets of these regions, respectively. C1a and C1b represent the first large cytoplasmic domain and C2a and C2b the second such intracellular domain. Bold sections indicate regions of high sequence homology among different cyclases. The N terminus (N) and a glycosylation site are also shown.



Figure 4.

Putative structure of cAMP‐dependent protein kinase, showing a regulatory subunit dimer and two catalytic subunits. The regulatory subunits show the two separate cAMP‐bindings sites (A and B), the autoinhibitory domain (including the autophosphorylation site for the type II enzyme), and the dimerization domain. The catalytic subunits show the binding sites for ATP and protein substrate.

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Article Title: Glucagon Signal‐Transduction Mechanisms
 

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J. H. Exton. Glucagon Signal‐Transduction Mechanisms. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 435-450. First published in print 2001. doi: 10.1002/cphy.cp070213