Membrane-targeting sequences on AKAP79 bind phosphatidylinositol-4, 5-bisphosphate

The EMBO Journal
Mark L Dell'AcquaJ D Scott

Abstract

Protein kinases and phosphatases are targeted through association with anchoring proteins that tether the enzymes to subcellular structures and organelles. Through in situ fluorescent techniques using a Green Fluorescent Protein tag, we have mapped membrane-targeting domains on AKAP79, a multivalent anchoring protein that binds the cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and protein phosphatase 2B, calcineurin (CaN). Three linear sequences termed region A (residues 31-52), region B (residues 76-101) and region C (residues 116-145) mediate targeting of AKAP79 in HEK-293 cells and cortical neurons. Analysis of these targeting sequences suggests that they contain putative phosphorylation sites for PKA and PKC and are rich in basic and hydrophobic amino acids similar to a class of membrane-targeting domains which bind acidic phospholipids and calmodulin. Accordingly, the AKAP79 basic regions mediate binding to membrane vesicles containing acidic phospholipids including phosphatidylinositol-4, 5-bisphosphate [PtdIns(4,5)P2] and this binding is regulated by phosphorylation and calcium-calmodulin. Finally, AKAP79 was shown to be phosphorylated in HEK-293 cells following stimulation of PKA and PKC, and activation of...Continue Reading

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Citations

Feb 23, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·S Jaken, P J Parker
Sep 1, 2005·Cellular and Molecular Neurobiology·Kensuke NinomiyaTakahisa Taguchi
Nov 19, 2003·Biochemical and Biophysical Research Communications·Kimberly L Dodge, John D Scott
Feb 21, 2004·Neuropharmacology·Andrea L BaumanJohn D Scott
Jun 29, 2002·Molecular and Cellular Endocrinology·M KovoN Dekel
Mar 14, 2000·Current Opinion in Cell Biology·A S Edwards, J D Scott
Oct 18, 2005·Nature Cell Biology·Naoto HoshiJohn D Scott
Jun 19, 2010·Nature Chemical Biology·Tatiana G Kutateladze
Dec 2, 2004·Nature Reviews. Molecular Cell Biology·Wei Wong, John D Scott
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Matthew G GoldJohn D Scott
May 21, 2010·The Journal of Biological Chemistry·Michael W FriedrichOliver Griesbeck
Jul 21, 2011·The Journal of Biological Chemistry·Ilse Delint-RamirezDermot M F Cooper
Dec 25, 2012·The Journal of Biological Chemistry·Riad EfendievCarmen W Dessauer
Sep 11, 2007·The Journal of Biological Chemistry·April S GoehringJohn D Scott
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