PHLPP Antibody – Rabbit Polyclonal

This gene encodes a member of the serine/threonine phosphatase family. The encoded protein promotes apoptosis by dephosphorylating and inactivating the serine/threonine kinase Akt, and functions as a tumor suppressor in multiple types of cancer. Increased expression of this gene may also play a role in obesity and type 2 diabetes by interfering with Akt-mediated insulin signaling. [provided by RefSeq, Dec 2011]

PHLPP: a pleckstrin homology domain leucine-rich repeat protein phosphoserine and ¿threonine phosphatase. A tumor suppressor that controls the onset and progression of various cancers because it controls the balance between cell survival and apoptosis. Catalyzes the dephosphorylation of the hydrophobic motif on the AGC kinases Akt, PKC, and S6 kinase, and the inhibitory site on the kinase Mst1. The dephosphorylation of PKCA and PKCB is destabilizing, leading to its degradation. The dephosphorylation of p70S6K at T390 reduces its activity, thus reducing the efficiency of protein translation. Dephosphorylation of Mst1 by PHLPP of an autoinhibitory site (T387) activates Mst1, resulting in the activation of the pro-apoptotic MAPK pathway. Ubiquitously expressed in non-cancerous tissues. Insensitive to inhibition by okadaic acid. PHLPP loss occurs at high frequency in colorectal cancer, and leads to the development of prostate tumors in mice. PHLPP degradation by the 26 S proteasome is controlled by a beta-TrCP-containing Skp¿Cullin 1¿F-box protein (SCF) complex E3 ubiquitin ligase in a phosphorylation-dependent manner. This degradation requires phosphorylation of PHLPP1 by CK I and GSK-3beta. Activation of the PI3K/Akt pathway suppresses the degradation of PHLPP1 by inhibiting GSK-3beta activity. PHLPP2 activity is highly sensitive to a common polymorphism (L-1016-S) that reduces its rate of dephosphorylation of the hydrophobic motif of Akt and PKC, rendering it ineffective at inducing apoptosis. This variant is expressed by 30% of the human population. Interacts with the nucleotide free form of KRas via its LRR repeats. Interacts with AKT2, AKT3 and PKCB isoform beta-II.

Protein type: Tumor suppressor; EC 3.1.3.16; Protein phosphatase, Ser/Thr (non-receptor)

Chromosomal Location of Human Ortholog: 18q21.33

Cellular Component: membrane; cytosol; nucleus

Molecular Function: protein binding; metal ion binding; phosphoprotein phosphatase activity

Biological Process: epidermal growth factor receptor signaling pathway; phosphoinositide-mediated signaling; fibroblast growth factor receptor signaling pathway; nerve growth factor receptor signaling pathway; dephosphorylation; apoptosis; innate immune response; entrainment of circadian clock