Abstract
Pleckstrin Homology Domain Leucine Rich Repeat Protein Phosphatases (PHLPP) are a pair of recently discovered PP2C‐type serine/threonine phosphatases in the PPM phosphatase family. They dephosphorylate the hydrophobic motifs of Akt at serine 473 and protein kinase C at serine 660. PHLPP has been shown to have a role in cancer cells but has not been studied in many other cell types. Overexpression of the protein in cancer cells causes increased apoptosis as well as reduced tumor size via downregulation of Akt signaling. To determine whether PHLPPs have a role in regulation of glucose homeostasis, we have performed glucose tolerance tests using wild type and whole body PHLPP1 knockout mice and found that mice lacking PHLPP1 have improved glucose tolerance compared to wild type. This may be due to increased insulin secretion or improved insulin action in the PHLPP1 knockout mice. Preliminary data suggest that PHLPP1/2 may play a role in regulation of insulin secretion in pancreatic beta cells. Experiments are under way to dissect the molecular mechanisms by which PHLPPs regulate insulin secretion and thereby influence glucose homeostasis. Supported by NIH grant R56 DK067581‐06
Published Version
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