AKAP95/AKAP8 Orchestrates and Synchronizes Cellular Events

Fri, 12/07/2012 - 11:58

A-kinase anchor proteins (AKAPs), such as AKAP95/AKAP8, are scaffold proteins that contain a binding domain for the RI/RII subunit of protein kinase A (PKA). AKAPs orchestrate and synchronize cellular events by tethering the cAMP-dependent PKA and other signaling enzymes to organelles and membranes. This gene encodes a nuclear A-kinase anchor protein that binds to the RII alpha subunit of PKA and may play a role in chromosome condensation during mitosis (1).

IHC analysis of IHC AKAP95/AKAP8 in human ovarian cancer

In a recent study the subcellular localization of human AKAP95 was examined throughout the HeLa cell cycle. Immunofluorescence analysis using an affinity-purified anti–AKAP95 antibody confirmed that AKAP95 was exclusively nuclear in interphase, and immunoblotting analysis of AKAP95 revealed similar levels of AKAP95 in whole interphase and mitotic cell lysates (2). AKAPs ensure correct spatial and temporal control of PKA action through the formation of multimolecular complexes that include specific upstream activators, select PKA substrates, and other signaling enzymes that participate in pathway cross talk. AKAPs not only anchor PKA but also act as scaffolding proteins that coordinate the activity of many other signaling enzymes such as kinases, phosphatases, phosphodiesterases, adenylyl cyclases, GTPases, and other regulatory proteins suggesting that AKAPs assemble multienzyme signaling complexes that ensure the integration and processing of multiple signaling pathways (3). As a result, these protein-protein interactions may create pockets of active kinases in situ leading to important consequences for drug discovery and research projects predicated on the selectivity of protein kinase inhibitors.

  1. PMID: 9473338
  2. PMID: 10601332
  3. PMID: 20495562

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