GRP94 Monoclonal Antibody (Clone 9G10)

Glucose regulated protein 94 (GRP94) is a constitutively expressed endoplasmic reticulum (ER) lumenal protein that is up-regulated in response to cellular stress such as heat shock, oxidative stress or glucose depletion. GRP94 is thought to play a role in protein translocation to the ER, in their subsequent folding and assembly, and in regulating protein secretion.¹ GRP94 also plays a role in antigen presentation by accessing the endogenous pathway and eliciting specific cytotoxic T lymphocyte (CTL) responses to chaperone bound peptides via the major histocompatibility complex (MHC) class I pathway.² GRP94 is a member of the Hsp90 family of stress proteins and shares sequence homology with its cytosolic equivalent, Hsp90.³ Both Hsp90 and GRP94 are calcium binding proteins.⁴ Despite sharing 50% sequence homology over its N domains and complete conservation in its ligand binding domains with Hsp90, GRP94, and Hsp90 differ in their interactions with regulatory ligands as GRP94 has weak ATP binding and hydrolysis activity.⁵ GRP94 exists as a homodimer and the two subunits interact at two distinct intermolecular sites, C-terminal dimerization domains and the N-terminal interacts with the middle domain of opposing subunits.⁶ GRP94 contains a carboxy terminal KDEL (Lys-Asp-Glu-Leu) sequence which is believed to aid in its retention in the ER.⁷

1.Ruddon, R.W., and Bedows, E.Assisted protein foldingThe Journal of Biological Chemisty272(6)3125-3128(1997) 2.Srivastava, P.K., Udono, H., Blachere, N.E., et al.Heat shock protein transfer peptides during antigen processing and CTL primingImmunogenetics39(2)93-98(1994) 3.Mazzarella, R.A., and Green, M.ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum, is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa glucose regulated protein (GRP94)The Journal of Biological Chemisty262(18)8875-8883(1987) 4.Kang, H.S., and Welch, W.J.Characterization and purification of the 94-kDa glucose-regulated proteinThe Journal of Biological Chemisty266(9)5643-5649(1991) 5.Soldano, K.L., Jivan, A., Nicchitta, C.V., et al.Structure of the N-terminal domain of GRP94. Basis for ligand specificity and regulationThe Journal of Biological Chemisty278(48)48330-48338(2003) 6.Chu, F., Maynard, J.C., Chiosis, G., et al.Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94Protein Science151260-1269(2006) 7.Peter, F., Van, P.N., and SÖling, H.D.Different sorting of Lys-Asp-Glu-Leu proteins in rat liverThe Journal of Biological Chemisty267(15)10631-10637(1992)