The mechanism by which RTKs number is Desacetyl-asperulosidic-acid regulated on cell surface is a balance between the rate of internalization and the rate of replacement. RTKs internalization is commonly triggered by ligand binding and occurs via clathrin coated pits, the first identified and best studied route for entry of RTKs into the cell. Clathrin-coated pits take part to IGF-IR internalization but recently it has been demonstrated that different plasma membrane micro-domains such as caveolae could regulate the biological actions of many plasma membrane receptors. We demonstrate that both Cav-1 and PTRF/Cavin regulate the surface expression of IGF-IR following IGF1treatment. Since Cav1 and PTRF/Cavin both regulate caveolae stability, the fact that Cav-1 and PTRF/Cavin reduce IGF-IR endocytosis could be explained by a reduction of caveolae observed in Cav-1 and PTRF/Cavin null cell. This effect could be due also to a structural change as hypothesized by others, or to a mislocalization of other caveolar proteins. For this reason alternative sources of b-cells from human pluripotent cells has been sought. Most of the protocols that have been established to drive pluripotent cells towards the b-cell lineage involve inducing the formation of a definitive endoderm enriched population by using Taltirelin Activin A, a member of the TGFb family of growth factors. From there the cells are directed down a differentiation pathway that mimics the events that occur in the developing mouse. The idea is to recapitulate the pattern of expression of key transcription factors, including Pdx1, Ngn3, NeuroD, Nkx6.1, Pax4, and MafA, that define the b-cell lineage. This approach has been validated by controlling the temporal expression of an exogenous Pdx1 gene in ES cells that have been stably transfected with a tetracycline responsive Pdx1 DNA construct. This ability to fine tune the activity of key transcription factors in a dose and time dependent manner may overcome some of the challenges in generating functional b-cells in vitro. Most cells are designed to prevent non-specific uptake of proteins. However, certain viruses have circumvented this by generating proteins that contain protein transduction domains. Thus the PTD of the HIV1-TAT protein has been exploited in cell engineering because of its effectiveness and small size, and TAT-fused proteins have been shown to be efficiently taken up by a variety of cells, including ES cells. In the present study we used PTD-mediated uptake of Pdx1 and MafA into DE-enriched mouse ES cells. These transcription factors were added in a manner that mimicked the temporal pattern of expression in the mouse embryo. The results showed that insulin expressing b-like cells could be generated.