DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20170189

RSK-dependent 14-3-3 interactions

Madhurima Saha

Abstract


14-3-3 proteins were identified as abundant proteins from bovine brain homogenates. They eluted at the 14th fraction from a two-dimensional DEAE-cellulose chromatography column and were the 3.3 band on the subsequent gel electrophoresis.1 14-3-3s were also given different names according to their novel roles in different organisms ranging from plants to animals as reviewed by Aitken.2 Physiologically, these are 30kDa acidic proteins and modulate other proteins in signal transduction pathways by binding to specific phospho-serine/threonine target motifs. The two highly preferred motifs recognized by 14-3-3 on their target proteins are R[S/Φ][+]pS/TXP (mode 1) and RX[S/Φ][+]pS/TXP (mode 2) where pS/T means phosphorylated serine or threonine, Φ means an aromatic residue, + is a basic residue and X is any type of an amino acid with a preference for Leu, Glu, Ala, Met.3 The regulation of multiple oncogenic proteins has spotlighted 14-3-3 as the central point of various signaling cues which govern cell proliferation, growth and tumor suppression.4 There are seven distinct isoforms in mammals (ζ, β, γ, η, σ, τ and ε), fifteen in plants and two each in D. melanogaster and C. elegans.5 They exist as homodimers and except for the sigma isoform which exists as heterodimers within the cell and can bind to more than one protein due to the dimerization of the monomers.12

Full Text:

PDF

References


Moore BW. Chemistry and Biology of Two Proteins, S-100 and 14-3-2, Specific to the Nervous System. In: Carl CP, John RS, eds. International Review of Neurobiology: Academic Press. 1972:215-25.

Aitken A. 14-3-3 proteins: A historic overview. Seminars in Cancer Biology. 2006;16:162-72.

Obsil T, Obsilova V. Structural basis of 14-3-3 protein functions. Seminars in Cell & Developmental Biology. 2011;22:663-72.

Wilker E, Yaffe MB. 14-3-3 Proteins—a focus on cancer and human disease. J Molec Cellul Cardio. 2004;37:633-42.

Dougherty MK, Morrison DK. Unlocking the code of 14-3-3. J Cell Sci. 2004;117:1875-84.

Anjum R, Blenis J. The RSK family of kinases: emerging roles in cellular signalling. Nat Rev Mol Cell Biol. 2008;9:747-58.

Galan JA, Geraghty KM, Lavoie G, Kanshin E, Tcherkezian J, Calabrese V1, et al. Phosphoproteomic analysis identifies the tumor suppressor PDCD4 as a RSK substrate negatively regulated by 14-3-3. Proc Natl Acad Sci USA. 2014;111(29):E2918-27.

Saha M, Carriere A, Cheerathodi M, Zhang X, Lavoie G, Rush J, et al. RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation. Biochem J. 2012;447(1):159-66.

Masters SC, Yang H, Datta SR, Greenberg ME, Fu H. 14-3-3 Inhibits Bad-Induced Cell Death through Interaction with Serine-136. Molecular Pharmacology. 2001;60:1325-31.

Stratford AL, Dunn SE. The promise and challenges of targeting RSK for the treatment of cancer. Expert Opinion on Therapeutic Targets. 2011;15:1-4.

Freeman AK, Morrison DK. 14-3-3 Proteins: Diverse Functions in Cell Proliferation and Cancer Progression. Seminars in cell and developmental biology. 2011;22:681-7.

Shen, Ying H. Significance of 14-3-3 Self-Dimerization for Phosphorylation-Dependent Target Binding.” Ed. Mark Ginsberg. Molecular Biology of the Cell. 2003:4721-33.

Rajalingam K, Schreck R, Rapp UR, Albert S. Ras oncogenes and their downstream targets, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2007;1773(8):1177-95.