Fat and muscle cells express large amounts of the insulin-responsive glucose transporter GLUT4

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#Unit 4. Cell Communication and Cell Signaling

The GPK in skeletal muscle is a huge protein with multiple subunits:

Kinase subunit contains the catalytic activity that activates GP 

Regulatory subunits is the ubiquitous protein calmodulin

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#Unit 4. Cell Communication and Cell Signaling

GPK enzyme activity is increased either by phosphorylation of these two regulatory subunits by PKA or by Ca+2 binding to the calmodulin subunit; maximal activity requires both.

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#Unit 4. Cell Communication and Cell Signaling

Phosphorylation of PKA at threonine-197 leads to conformational change in the activation loop, that promotes binding of both ATP and its substrate proteins.

PKA can autophosphorylate itself on T197

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#Unit 4. Cell Communication and Cell Signaling

The activities of GPK and GP are inhibited by a phosphatase called phosphoprotein phosphatase.

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#Unit 4. Cell Communication and Cell Signaling

The promoter or enhancer segments of all genes regulated by PKA contain a cis-acting DNA sequence, the cAMP-response element (CRE), which

contains the highly conserved nucleotide sequence,

5'-TGACGTCA-3'.

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#Id: 9066

#Unit 4. Cell Communication and Cell Signaling

In nucleus PKA phosphorylate serine-133 on a transcription factor called CREbinding (CREB) protein