Raf kinase activation of adenylyl cyclases: isoform-selective regulation.

@article{Ding2004RafKA,
  title={Raf kinase activation of adenylyl cyclases: isoform-selective regulation.},
  author={Qingming Ding and Robert Gros and Ian D Gray and Ronald Taussig and Stephen S. G. Ferguson and Ross D Feldman},
  journal={Molecular pharmacology},
  year={2004},
  volume={66 4},
  pages={
          921-8
        }
}
Adenylyl cyclases (AC), a family of enzymes that catalyze the synthesis of cyclic AMP, are critical regulators of cellular functions. [] Key Result In human embryonic kidney 293 cells, we now demonstrate that in reconstitution studies, c-Raf kinase can mediate phosphorylation of AC VI. Furthermore, AC VI coimmunoprecipitates with c-Raf. Raf kinase-dependent regulation of adenylyl cyclase VI is dependent on the integrity of Ser750 in the fourth intracellular loop of the enzyme and Ser603/Ser608 in the C1b…

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References

SHOWING 1-10 OF 25 REFERENCES
Tyrosine kinase-mediated serine phosphorylation of adenylyl cyclase.
TLDR
It is shown that the tyrosine kinase-dependent enhancement of adenylyl cyclase isoform VI function parallels an enhancement in serine phosphorylation of the enzyme, and this enhancement was not attenuated by inhibitors of ERK, PKC, PKA, or PI3 kinase activity but was blunted by inhibition of endogenous p74(raf-1)() activity.
Adenylyl cyclase 6 is selectively regulated by protein kinase A phosphorylation in a region involved in Galphas stimulation.
  • Y. Chen, A. Harry, R. Iyengar
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
TLDR
PKA treatment of recombinant AC6 in insect cell membranes results in a selective loss of stimulation by high (>10 nM) concentrations of Galphas, suggesting a mechanism of how isoform selective regulatory diversity can be obtained within conserved regions involved in signal communication.
Protein Kinase C Alters the Responsiveness of Adenylyl Cyclases to G Protein α and βγ Subunits*
TLDR
It is demonstrated that protein kinases can alter both the activity of adenylyl cyclase isoforms and their responsiveness to G protein regulation, thereby altering the ability of adenosine cyclase to integrate signals derived from multiple hormonal inputs.
Adenylyl cyclase type II is stimulated by PKC via C-terminal phosphorylation.
Protein Kinase C Inhibits Adenylyl Cyclase Type VI Activity during Desensitization of the A2a-Adenosine Receptor-mediated cAMP Response*
TLDR
It is demonstrated that a calcium-independent, novel PKC inhibits AC6 activity during A2a desensitization in PC12 cells, providing an exquisite mechanism for integrating signaling pathways to fine-tune cAMP synthesis.
Regulation and role of adenylyl cyclase isoforms.
TLDR
The present review deals with various aspects of regulations, emphasizing the role of calcium/calmodulin in activating AC1 and AC8 in the central nervous system, the potential inhibitory effect of calcium on AC5 and AC6, and the changes in the expression pattern of the isoforms during development.
Protein Kinase C Inhibits Type VI Adenylyl Cyclase by Phosphorylating the Regulatory N Domain and Two Catalytic C1 and C2 Domains*
TLDR
It is proposed that the three cytosolic domains of ACVI might form a regulatory complex and phosphorylation of this regulatory complex at different sites might induce a fine-tuning of the catalytic core complex and subsequently lead to alternation in the catalysttic activity of AC VI.
Involvement of Raf-1 in chronic delta-opioid receptor agonist-mediated adenylyl cyclase superactivation.
Lowered responsiveness of the catalyst of adenylyl cyclase to stimulation by GS in heterologous desensitization: a role for adenosine 3',5'-monophosphate-dependent phosphorylation.
TLDR
Data indicate that one component of hormone-induced desensitization of the adenylyl cyclase system can be at the level of the catalyst, where PKA-mediated phosphorylation could result in lowered responsiveness.
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