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Osmanagic-Myers S, Wiche GPlectin-RACK1 (receptor for activated C kinase 1) scaffolding: a novel mechanism to regulate protein kinase C activity. J Biol Chem 279:18701-18710

Institute of Biochemistry and Molecular Cell Biology, University of Vienna, Vienna Biocenter, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
Journal of Biological Chemistry (Impact Factor: 4.57). 05/2004; 279(18):18701-10. DOI: 10.1074/jbc.M312382200
Source: PubMed

ABSTRACT Agonist-induced translocation of protein kinase C (PKC) isozymes is mediated by receptors for the activated form of the kinase, shuttling it from one intracellular site to another and enhancing its catalytic activity. It is however unknown whether the receptors themselves are anchored to certain intracellular structures prior to their engagement with PKC. We show here sequestering of receptor for activated C kinase 1 (RACK1) to the cytoskeleton through the cytoskeletal linker protein plectin during the initial stages of cell adhesion. We found that upon PKC activation, RACK1 was released from the cytoskeleton and transferred to the detergent-soluble cell compartment, where it formed an inducible triple complex with one of the PKC isozymes, PKCdelta, and with plectin. In plectin-deficient cells the cytoskeleton-associated RACK1 fraction was reduced, and the protein was found predominantly at sites to which it normally translocated upon PKC activation. Concomitantly, dislocation of PKCdelta and elevated enzymatic activity were observed in these cells. PKCdelta was also more rapidly degraded, likely due to its overactivation. We propose a previously unrecognized function of plectin as cytoskeletal regulator of PKC signaling, and possibly other signaling events, through sequestration of the scaffolding protein RACK1.

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    • "Plectin is an intermediate filament (IF)-associated linker protein that also functions to regulate actin dynamics and serves as a scaffold for signaling proteins. RACK1-Plectin interactions are particularly important in recruiting and maintaining kinases at the IF cytoskeleton, regulating keratin architecture, adhesion and migration in epithelial cells [32,33]. The RACK1-Keratin interaction is also important in regulation of PKCalpha activity and stabilisation of desmosomes to control intercellular adhesion [34]. "
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    Cell Communication and Signaling 08/2013; 11(1):53. DOI:10.1186/1478-811X-11-53 · 4.67 Impact Factor
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    • "In myofibers, the contractile apparatus is suspended in a network of desmin filaments linked to the nuclear envelope and the sarcoplasmatic reticulum via plectin isoform 1 (P1), to sarcolemmal costameres and Z-disks via P1f and P1d, respectively, and to mitochondria via P1b [7-9]. Apart from functioning as structural reinforcement and organizing elements of the cytoskeleton, plectin isoforms play also an important role as scaffolding platforms for signaling proteins involved in cell metabolism, stress response, and motility [10-13]. "
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    Skeletal Muscle 06/2013; 3(1):14. DOI:10.1186/2044-5040-3-14
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    • "Lately, it has become clear that plectin, in addition to structurally reinforcing the cytoskeleton, acts as a scaffold for molecules and proteins involved in signaling, by positioning them at specific sites within the cells. Examples are the signaling molecule phosphatidylinositol-4,5-bisphosphate (PIP2; involved in the interaction of plectin with actin; Andrä et al. 1998), the nonreceptor tyrosine kinase Fer (requires plectin to turn down its autophosphorylation; Lunter and Wiche 2002), the receptor for activated C kinase 1 (RACK1; when bound to plectin downregulates PKC signaling during the initial stages of cell adhesion; Osmanagic-Myers and Wiche 2004), the γ-subunit of AMP-activated protein kinase (AMPK; associates with Z-disk-bound plectin in differentiated myofibers; Gregor et al. 2006), components of the MAP kinase Erk 1/2 signaling pathway (required for controlled cell migration; Osmanagic-Myers et al. 2006), the chemokine receptor CXCR4 (plays an important role in stromal-derived factor-1 signaling and trafficking, and in HIV-1 infection; Ding et al. 2008), the RON receptor (a member of the Met proto-oncogen family frequently overexpressed in pancreatic cancer; Yu et al. 2012), and the NR3a subunit of the glutamate receptor (Eriksson et al. 2007). "
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