Abstract

This application focuses on the mechanism by which A-kinase anchoring proteins (AKAPs), and more specifically AKAP79, promotes the cellular compartmentalization of protein kinases and phosphatases down-stream of receptors that activate them and upstream of target proteins.
Aim 1 will elucidate the functional consequences of AKAP79-mediated targeting of PKA to the beta2-adrenergic receptor and map sites of interaction on both the receptor and the anchoring protein.
In Aim 2, a combination of biochemical and electrophysiological approaches will be used to examine whether AKAP79-mediated anchoring of PKA and PP-2B close to the AMPA channel augments or attenuates channel activity by promoting its phosphorylation or dephosphorylation, respectively.
In Aim 3, experiments are proposed to determine if the interaction of AKAP79 with PSD95, an integral component of the postsynaptic density, links upstream signaling complexes with downstream elements such as NMDA or AMPA glutamate receptors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM048231-09
Application #
6095321
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Jones, Warren
Project Start
1992-08-01
Project End
2004-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
9
Fiscal Year
2000
Total Cost
$214,420
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Murphy, Jonathan G; Sanderson, Jennifer L; Gorski, Jessica A et al. (2014) AKAP-anchored PKA maintains neuronal L-type calcium channel activity and NFAT transcriptional signaling. Cell Rep 7:1577-1588
Mercado, Jose; Baylie, Rachael; Navedo, Manuel F et al. (2014) Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle. J Gen Physiol 143:559-75
Gold, Matthew G; Fowler, Douglas M; Means, Christopher K et al. (2013) Engineering A-kinase anchoring protein (AKAP)-selective regulatory subunits of protein kinase A (PKA) through structure-based phage selection. J Biol Chem 288:17111-21
Smith, F Donelson; Scott, John D (2013) Scaffolding proteins: not such innocent bystanders. Curr Biol 23:R515-7
Scott, John D; Dessauer, Carmen W; Tasken, Kjetil (2013) Creating order from chaos: cellular regulation by kinase anchoring. Annu Rev Pharmacol Toxicol 53:187-210
Smith, F Donelson; Reichow, Steve L; Esseltine, Jessica L et al. (2013) Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation. Elife 2:e01319
Hinke, Simon A; Navedo, Manuel F; Ulman, Allison et al. (2012) Anchored phosphatases modulate glucose homeostasis. EMBO J 31:3991-4004
Havekes, Robbert; Canton, David A; Park, Alan J et al. (2012) Gravin orchestrates protein kinase A and ?2-adrenergic receptor signaling critical for synaptic plasticity and memory. J Neurosci 32:18137-49
Kosenko, Anastasia; Kang, Seungwoo; Smith, Ida M et al. (2012) Coordinated signal integration at the M-type potassium channel upon muscarinic stimulation. EMBO J 31:3147-56
Altier, Christophe; Dubel, Stefan J; Barrere, Christian et al. (2012) AKAP79 modulation of L-type channels involves disruption of intramolecular interactions in the CaV1.2 subunit. Channels (Austin) 6:157-65

Showing the most recent 10 out of 29 publications