Biopolymers and cell. 2007; 23 (4): 318 - 323

Interaction of serine/threonine protein phosphatase 5 with the protein products of tumour suppressor gene Tsc2

O. M. Malanchuk, S. S. Palchevskyy, V. K. Pozur, I. T. Gout , V. V. Filonenko

Tuberous sclerosis (TSC) is a tumour disease caused by mutations in Tsc1 or Tsc2 genes. Both protein products of Tsc1 and Tsc2 form an intracellular complex possessing GTPase-activating (GAP) activity towards a small GTP binding protein Rheb. The activity of TSC1/2 complex is regulated by multiple phosphorylations of TSC2 mediated by several kinases, such as PKB/Akt, AMP-activated kinase (AMPK), ERK, MK2 and RSK1. So far, very little is known about the molecular mechanisms of TSC2 dephosphorylation. In the yeast two-hybrid screening, we have identified a number of potential TSC2 binding partners including protein phosphatase 5 (PP5). In this study, we provide the evidence that the interaction between TSC2 and PP5 also occurs in mammalian cells. Using TSC2+/+, p53–/– mouse embryo fibroblasts (MEFs) transiently overexpressing myc-PP5, we showed in the immunoprecipitation assay that TSC2 specifically associates with myc-PP5 in exponentially growing cells. The physiological relevance of identified interaction, especially the involvement of PP5 in the dephosphorylation of major regulatory sites is currently under investigation.

Keywords: TSC2, tuberous sclerosis, PP5, protein-protein interactions.