Anti-Glucose Regulated Protein 78 (Grp78, BiP)(grp78, BiP, GRP 78)

Within the ER misfolded proteins are detected by Bip (GPR78). In the presence of misfolded proteins, Bip disscociates from PERK, allowing it to homodimerize and autophosphorylate. In its dimerized, phosphorylated form PERK phosphorylates eIF2. The phosphorylation of eIF2 blocks the majority of translation to prevent the continued accumulation of protein in the ER. , Bip also is binds to IRE1 and ATF6 under normal ER conditions, but dissociates upon accumulation of misfolded proteins. Unbound ATF6 is translocated to the gogli where it is converted into a cleaved, active form. The cleaved form of ATF6 is then able to up-regulate transcription of UPR genes including XBP1. Activated IRE1 acts as an endoribonuclease to an intron from XBP1 transcripts. The XBP1 splice variant codes for an active transcription factor which activates transcription of P58IPK. P58IPK is a HSP40 protein which binds to and inhibits PERK. Thus, if the accumulated, misfolded proteins have been removed, P58IPK acts to shut down the UPR by removing the block to translation. Applications: Suitable for use in Western Blot. Other applications not tested. Recommended Dilution: Western Blot: 2ug/ml, Optimal dilutions to be determined by the researcher. Positive Control: Rat liver extract, Storage and Stability: May be stored at 4°C for short-term only. For long-term storage, aliquot and store at -20°C. Aliquots are stable for at least 12 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.