phop70S6K and phospho rpS6 were significantly suppressed in all sub lines tested

Mutational analysis of PTEN unmasked that the lipid phosphatase activity of PTEN is needed for this PTEN dependent cell size checkpoint, while the capacity of PTEN to regulate Akt phosphorylation is dispensable for this checkpoint. This was subsequently confirmed with using Akt inhibitors. Endogenous PTEN was shown to interact in the membrane with Tipifarnib an actin remodeling complex that contains actin remodeling proteins, for example gelsolin, a protein considered to be regulated by PIP2. Therapy of PTEN cells with cytochalasin D, a potent inhibitor of actin remodeling, resulted in abrogation of the cell size checkpoint. Essentially, this inhibitor produced no effect on cell size control in normally isogenic PTEN cells. Taken together, these data suggest that immediate control Endosymbiotic theory of actin remodeling but not control of Akt phosphorylation is necessary for PTEN dependent cell size checkpoint control. It was surprising to us that the PTEN dependent size phenotype described herein was Akt independent, since there are numerous stories in the literature of Akt being fully a central player in cell size get a grip on. In N. melanogaster, activation of Akt contributes to increased cell and organ growth, and regulation of Akt seems to be necessary for the results of PTEN on cell and organ size. Akt has also been shown to promote cell and organ growth in rats, although presence of multiple Akt homologs has difficult testing its epistasis with PTEN. We do not understand the molecular basis of the discrepancies between these types of published studies and the information presented herein. Possible answers include mechanistic differences between cell size control all through organismal growth and DNA damage induced Gemcitabine cell cycle arrest, mechanistic differences in cell size control between people, mice, and flies, and/or the possibility that Akt and PTEN function in parallel pathways to control cell size. Currently, PTEN could be the only known major regulator of the DNA damage caused cell size checkpoint. It is worth noting, nevertheless, that the selection of genes, such as the S6K, LK6, TSC1, and TSC2 genes and myc, have already been demonstrated to regulate cell size all through growth. The fact that many of these genes are cancer-related raises the important question whether the abrogation of cell size checkpoint control is essential to neoplastic transformation in a manner similar to that of abrogation of the G1 and G2 checkpoints. Obviously, many cytopathological findings that contained in PTEN deficient cancers tend because of defective PTEN dependent cell size gate get a grip on. The clear presence of giant cells in tumors and the existence of tumor types that are composed exclusively of enlarged cells are two such cytopathological presentations. Despite these findings, whether abrogation of cell size gate get a grip on actually pushes neoplasia is not clear. Because Akt is thought to be an integral effector of PTEN dependent tumor withdrawal but is clearly dispensable for cell size checkpoint get a handle on inside the systems examined here, the cell size checkpoint may not be related to driving neoplasia.