+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Scaffolding by A-kinase anchoring protein enhances functional coupling between adenylyl cyclase and TRPV1 channel

Scaffolding by A-kinase anchoring protein enhances functional coupling between adenylyl cyclase and TRPV1 channel

Journal of Biological Chemistry 288(6): 3929-3937

Scaffolding proteins often bring kinases together with their substrates to facilitate cell signaling. This arrangement is critical for the phosphorylation and regulation of the transient receptor potential vanilloid 1 (TRPV1) channel, a key target of inflammatory mediators such as prostaglandins. The protein kinase A anchoring protein AKAP79/150 organizes a multiprotein complex to position protein kinase A (PKA) and protein kinase C (PKC) in the immediate proximity of TRPV1 channels to enhance phosphorylation efficiency. This arrangement suggests that regulators upstream of the kinases must also be present in the signalosome. Here, we show that AKAP79/150 facilitates a complex containing TPRV1 and adenylyl cyclase (AC). The anchoring of AC to this complex generates local pools of cAMP, shifting the concentration of forskolin required to attenuate capsaicin-dependent TRPV1 desensitization by ∼100-fold. Anchoring of AC to the complex also sensitizes the channel to activation by β-adrenergic receptor agonists. Significant AC activity is found associated with TRPV1 in dorsal root ganglia. The dissociation of AC from an AKAP150-TRPV1 complex in dorsal root ganglia neurons abolishes sensitization of TRPV1 induced by forskolin and prostaglandin E(2). Thus, the direct anchoring of both PKA and AC to TRPV1 by AKAP79/150 facilitates the response to inflammatory mediators and may be critical in the pathogenesis of thermal hyperalgesia.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 055656259

Download citation: RISBibTeXText

PMID: 23264624

DOI: 10.1074/jbc.m112.428144

Related references

The A-kinase anchoring protein Yotiao facilitates complex formation between adenylyl cyclase type 9 and the IKs potassium channel in heart. Journal of Biological Chemistry 287(35): 29815-29824, 2012

Adenylyl cyclase--A-kinase anchoring protein complexes: the next dimension in cAMP signaling. Molecular Pharmacology 76(5): 935-941, 2009

The A-kinase anchoring protein Yotiao binds and regulates adenylyl cyclase in brain. Proceedings of the National Academy of Sciences of the United States of America 105(37): 13835-13840, 2008

Adenylyl cyclase anchoring by a kinase anchor protein AKAP5 (AKAP79/150) is important for postsynaptic β-adrenergic signaling. Journal of Biological Chemistry 288(24): 17918-17931, 2013

Gonadotropin-releasing hormone inhibits pituitary adenylyl cyclase-activating polypeptide coupling to 3',5'-cyclic adenosine-5'-monophosphate pathway in LbetaT2 gonadotrope cells through novel protein kinase C isoforms and phosphorylation of pituitary adenylyl cyclase-activating polypeptide type I receptor. Endocrinology 149(12): 6389-6398, 2008

A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain 138(3): 604-616, 2008

Colocalization of protein kinase A with adenylyl cyclase enhances protein kinase A activity during induction of long-lasting long-term-potentiation. Plos Computational Biology 7(6): E1002084, 2011

Protein kinase C antagonizes pertussis-toxin-sensitive coupling of the calcitonin receptor to adenylyl cyclase. European Journal of Biochemistry 262(1): 95-101, 1999

Persistent Electrical Activity in Primary Nociceptors after Spinal Cord Injury Is Maintained by Scaffolded Adenylyl Cyclase and Protein Kinase A and Is Associated with Altered Adenylyl Cyclase Regulation. Journal of Neuroscience 36(5): 1660-1668, 2016

A kinase-anchoring proteins and adenylyl cyclase in cardiovascular physiology and pathology. Journal of Cardiovascular Pharmacology 58(4): 339-344, 2011

Chronic treatment of C6 glioma cells with antidepressant drugs increases functional coupling between a G protein (G-s) and adenylyl cyclase. Journal of Neurochemistry 64(2): 724-732, 1995

Developmental expression of the protein kinase C substrate/binding protein (clone 72/SSeCKS) in rat testis: identification as a scaffolding protein containing an A-kinase-anchoring domain which is expressed during late-stage spermatogenesis. European Journal of Biochemistry 263(3): 797-805, 1999