Protein kinase A signaling cascade ; GO:0010737

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PROTEIN KINASE A SIGNALING

See Figure 2 in: http://www.landesbioscience.com/curie/chapter/5438/

ACTIVATION OF PKA

PKA (cAMP-Dependent Protein Kinase) is known to mediate signal transduction downstream of G-protein-coupled receptors, and is activated by adenyl cyclase (AC)-generated cAMP.

PKA consists of two regulatory subunits, which function to maintain two catalytic subunits in an inactive status. When the regulatory units are activated by cAMP, the catalytic units are released as active holoenzymes.

DOWNSTREAM TARGETS OF PKA

• Cα (catalytic subunit alpha) phosphorylates cAMP-response element binding protein (CREB)
• Cβ (catalytic subunit beta) phosphorylates c-REL, a subunit of nuclear factor κB (NF-κB).

• PKA also acts in a negative feedback loop: PKA phosphorylates the phosphodiesterase that cleaves cAMP, leading to a rapid turnoff in a cAMP signal.

REFERENCES

PMID 20188216 (review)

QUESTIONS

• Where does the PKA signaling start and stop? Does it start with the cell-surface receptor (i.e. include any intracellular signaling events that go THROUGH PKA?)

This is an example of a pathway that goes through a single mediator. Upstream are the ligands, GPCRs, G-proteins, primary effectors (AC). Downstream are the target proteins.