RESUMO
To introduce self-organization ability of transmembrane proteins into Langmuir (L) and Langmuir-Blodgett (LB) techniques, we focused on "amphiphilic peptide" (AP) which is composed of two distinct hydrophilic and hydrophobic domains. Three types of APs of different average hydropathies were used to prepare the AP/lipid mixed L and LB films. According to the circular dichroism spectra, the secondary structures of APs were not uniform but were a mixture of alpha-helix, beta-strand and random coil. The fraction of alpha-helix was higher for lower hydropathy AP. The interaction between AP and lipid in the L film and the structure of the LB film were also depended on the APs used.
Assuntos
Cristalização/métodos , Bicamadas Lipídicas/química , Membranas Artificiais , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Peptídeos/química , Tensoativos/química , Teste de Materiais , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
GSK-3 is a serine/threonine kinase involved in a diverse range of cellular processes. GSK-3 exists in two isoforms, GSK-3α and GSK-3ß, which possess some functional redundancy but also play distinct roles depending on developmental and cellular context. In this article, we found that GSK-3 actively promoted cell growth and survival in melanoma cells, and blocking this activity with small-molecule inhibitor SB216763 or gene-specific siRNA decreased proliferation, increased apoptosis, and altered cellular morphology. These alterations coincided with loss of PAX3, a transcription factor implicated in proliferation, survival, and migration of developing melanoblasts. We further found that PAX3 directly interacted with and was phosphorylated in vitro on a number of residues by GSK-3ß. In melanoma cells, direct inhibition of PAX3 lead to cellular changes that paralleled the response to GSK-3 inhibition. Maintenance of PAX3 expression protected melanoma cells from the anti-tumor effects of SB216763. These data support a model wherein GSK-3 regulates proliferation and morphology of melanoma through phosphorylation and increased levels of PAX3.