Phosphoprotein Phosphatase 1 Isoforms Alpha and Gamma Respond Differently to Prodigiosin Treatment and Present Alternative Kinase Targets in Melanoma Cells

Margarida Fardilha, João Figueiredo, Margarita Espona-Fiedler, Juliana Felgueiras, Luís Korrodi-Gregório, Sara L. C. Esteves, Sandra Rebelo, Odete A. B.da Cruz Silva, Edgar da Cruz e Silva, Ricardo Pérez-Tómas

Department of Pathology and Experimental Therapeutics, Cancer Cell Biology Research Group, University of Barcelona, Barcelona, Spain.
Laboratory of Neuroscience, Centre for Cell Biology, Biology Department and Health Sciences Department, University of Aveiro, Aveiro, Portugal.
Laboratory of Signal Transduction, Centre for Cell Biology, Biology Department and Health Sciences Department, University of Aveiro, Aveiro, Portugal.

DOI: 10.4236/jbpc.2014.52008                

Abstract

Reversible protein phosphorylation is a central regulatory mechanism of cell function. Deregulation of the balanced actions of protein kinases and phosphatases has been frequently associated with several pathological conditions, including cancer. Many studies have already addressed the role of protein kinases misregulation in cancer. However, much less is known about protein phosphatases influence. Phosphoprotein Phosphatase 1 (PPP1) is one of the major serine/threonine protein phosphatases who has three catalytic isoforms: PPP1CA, PPP1CB, and PPP1CC. Its function is achieved by binding to regulatory subunits, known as PPP1-interacting proteins (PIPs), which may prefer a catalytic isoform. Also, some inhibitors/enhancers may exhibit isoform specificity. Here we show that, prodigiosin (PG), a molecule with anticancer properties, promotes the formation of PPP1CA-AKT complex and not of PPP1CC-MAPK complex. Both, AKT and MAPK, are well-known PIPs from two pathways that crosstalk and regulate melanoma cells survival. In addition, the analysis performed using surface plasmon resonance (SPR) technology indicates that PPP1 interacts with obatoclax (OBX), a drug that belongs to the same family of PG. Overall, these results suggest that PG might, at least in part, act through PPP1C/PIPs. Also, this study is pioneer in demonstrating PPP1 isoform-specific modulation by small molecules.

Keywords

Phosphoprotein Phosphatase 1 Catalytic Subunit, Surface Plasmon Resonance, Mitogen-Activated Protein Kinase, V-Akt Murine Thymoma Viral Oncogene, Glycogen Synthase Kinase 3

Conflicts of Interest

The authors declare no conflicts of interest.

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