In silico analysis of Kibra and STK4 as main components of Hippo Pathway in Sea Urchins

Hippo pathway controls organ size through the regulation of cell proliferation and apoptosis. Perturbation of upstream components of the Hippo pathway leads to tissue overgrowth and enlarged organ size without major changes in organ patterning. First discovered in Drosophila, many of Hippo pathway components have been identified in mammals. At the central core of the signalling cascade are MST1/2 kinases, two Hpo homologs in mammals. Mst1/2 are part of a conserved kinase cassette that, regulating downstream transcription coactivators YAP and TAZ, promote tissue proliferation, self-renewal of normal and cancer stem cells, migration, and carcinogenesis (1, 2). Recent studies have identified KIBRA (WWC1) as an upstream regulator of the Hippo pathway in Drosophila and mammals. Kibra/KIBRA is a cytoplasmic protein that acts by binding to Mer/NF2, and their co-expression results in synergistic phosphorylation of Warts (Lats1/2)(3,4). We have identified orthologous candidate Kibra and STK3/4 (MST1/2)proteins in the sea urchin Strongylocentrotus purpuratus.Sea urchin predicted Kibra and STK4contain canonical domains and share protein structures with the H.sapiens and D.melanogaster counterparts. Multiple sequence alignments were showing high identity scores in both protein and nucleotide sequences between S.purpuratus and other species. The analysis of intron-exon organization between S.purpuratus and Paracentrotus lividus(Mediterranean sea urchin) Kibra and STK4 genes, allowed to determine that genomic structure is well conserved between the two species. Analyses obtained by the estimation of the derived phylogenetic trees,showed that sea urchin Kibra and STK4 were highly similar to related proteins of the Deuterostome group.