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C2. Protein Kinase A (PKA)

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    Cascade of events: A transmembrane receptor WITHOUT ENZYMATIC ACTIVITY binds an extracellular chemical signal, causing a conformational change in the receptor which propagates through the membrane. The intracellular domain of the receptor is bound to an intracellular heterotrimeric G protein (since it binds GDP/GTP) in the cell. The G protein dissociates and one subunit interacts with and activates an enzyme - adenylate cyclase- which converts ATP into a second messenger - cyclic AMP (cAMP) - in the cell. cAMP activates protein kinase A (PKA) which phosphorylates proteins at specific Ser or Thr side chains.

    Figure: cyclic AMP


    Receptors which work through an intermediary G protein usually are single polypeptide chains that span the membrane seven times in a serpentine fashion.



    iconChime.gifUpdated Gs-alpha/adenylate cyclase complex Jmol14 (Java) | JSMol (HTML5)

    Some signals that activate adenylate cyclase and use cAMP as a second messenger include: corticotrophn, dopamine, epinephrine (β-adrenergic), follicle-stimulating hormone, glucagon, many odorants, prostaglandins E1and E2, and many tastants.

    Some enzymes regulated by cAMP-dependent phosphorylation by PKA
    Enzyme Pathway
    Glycogen Synthase glycogen synthesis
    Phosphorylase Kinase glycogen breakdown
    Pyruvate Kinase Glycolysis
    Pyruvate Dehydrogensae Pyruvate to acetyl-CoA
    Hormone-sensitive Lipase Triacylglyeride breakdown
    Tyrosine Hydroxylase Synthesis of DOPA, dopamine, norepinephrine
    Histone H1 Nucleosome formation with DNA
    Histone H2B Nucleosome formation with DNA
    Protein phosphatase 1 Inhibitor 1 Regulation of protein dephosphorylation
    CREB cAMP regulation of gene expression
    PKA cosensus sequence XR(R/K)X(S/T)B (B = hydrophobic amino acid)

    An example of how epinephrine (a flight/fight hormone) can lead to breakdown of glycogen (your main carbohydrate reserves in muscle and liver) is shown below. A cascade of events, starting with the binding of the hormone to its receptor, followed by activation of adenylate cyclase, which forms cAMP, which activates PKA, which leads to the activation of the enzyme that breaks down glycogen (glycogen phosphorylase) is shown. (For simplicity, G protein involvement is not shown.)

    Figure: Activation of glycogen phosphorylase through activation of PKA.


    C2. Protein Kinase A (PKA) is shared under a CC BY-NC-SA license and was authored, remixed, and/or curated by Henry Jakubowski.

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