title: Annexins - scaffolds modulating PKC localization and signaling.
abstract: Spatial and temporal organization of signal transduction is critical to link different extracellular stimuli with distinct cellular responses. A classical example of hormones and growth factors creating functional diversity is illustrated by the multiple signaling pathways activated by the protein kinase C (PKC) family of serine/threonine protein kinases. The molecular requirements for diacylglycerol (DAG) and calcium (Ca(2+)) to promote PKC membrane translocation, the hallmark of PKC activation, have been clarified. However, the underlying mechanisms that establish selectivity of individual PKC family members to facilitate differential substrate phosphorylation and varied signal output are still not fully understood. It is now well believed that the coordinated control and functional diversity of PKC signaling involves the formation of PKC isozyme-specific protein complexes in certain subcellular sites. In particular, interaction of PKC isozymes with compartment and signal-organizing scaffolds, including receptors for activated C-kinase (RACKs), A-kinase-anchoring proteins (AKAPs), 14-3-3, heat shock proteins (HSP), and importins target PKC isozymes to specific cellular locations, thereby delivering PKC isozymes into close proximity of their substrates. In addition, several annexins (Anx), including AnxA1, A2, A5 and A6, display specific and distinct abilities to interact and promote membrane targeting of different PKC isozymes. Together with the ability of annexins to create specific membrane microenvironments, this is likely to enable PKCs to phosphorylate certain substrates and regulate their downstream effector pathways in specific cellular sites. This review aims to summarize the capacity of annexins to modulate the localization and activity of PKC family members and participate in the spatiotemporal regulation of PKC signaling in health and disease.
authors.affiliation: Faculty of Pharmacy A15, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Monira
authors.initials: M
authors.lastname: Hoque
authors.affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Rentero
authors.affiliation: Faculty of Pharmacy A15, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Rose
authors.initials: R
authors.lastname: Cairns
authors.affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
authors.affiliation: Faculty of Pharmacy A15, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: thomas.grewal@sydney.edu.au.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grewal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017302:Annexins / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D017302:Annexins; D007527:Isoenzymes; D011493:Protein Kinase C
keywords: Annexins; PKC; Scaffold; Signal transduction