The 170 kDa glucose regulated stress protein is a large HSP70‐ HSP110‐like protein of the endoplasmic reticulum

Abstract

The existence of a family of unusually large and highly diverged hsp70-1ike proteins (the hspll0/SSE family) has recently been described. The 170 kDa glucose regulated stress protein (grpl70) is a retained endoplasmic reticulum glycoprotein that may be involved in immunoglobulin folding and/or assembly. We describe here the cloning of the cDNA for grpl70 and show that it, like hspll0, is a large and highly diverged hsp70-1ike polypeptide which shares specific features with hsp70 (the dnaK family) and the hspll01SSE family, while also differing from both. Grpl70 contains an ATP binding domain and binds ATP, it possesses a carboxyl terminal NDEL sequence, and its mRNA is anoxia inducible.

Characterization of Heat Shock Protein 110 and Glucose-Regulated Protein 170 as Cancer Vaccines and the Effect of Fever-Range Hyperthermia on Vaccine Activity

“…Hsp110 and grp170 both appear to exhibit a peptide-binding cleft (11,18,44). However, hsp110 and grp170 differ dramatically from the hsc70s in their C-terminal domains, which, in the case of hsc70 proteins, appear to function as a "lid" for the peptide-binding cleft and may have an important influence on the properties of the bound peptide/protein and/or the affinity for the associated peptide/ protein.…”

“…Less is understood at the molecular level of grp170 structure and function; however, cellular studies have shown that it binds to Ig chain in the ER, may be the ATPase responsible for protein import into the ER, and actively binds peptides from TAP (i.e., the transporter associated with Ag processing; Refs. 11,19,20,23,24).…”

“…The principal grps on the basis of expression have approximate sizes of 78 kDa (grp78), 94 kDa (grp94), and 170 kDa (grp170). grp78 is homologous to cytoplasmic hsp70, whereas grp94 is homologous to hsp90 (10,11). Although individual stress proteins have been studied for several years (in some cases intensively studied, e.g., hsp70), the largest of the above hsp and grp groups, hsp110 and grp170, have been almost entirely ignored.…”

“…Curiously, they have both been found by sequence analysis to represent large and highly "diverged" relatives of the hsp70 family. It is recognized today that the hsp70 "family," the hsp110 family, and the grp170 family comprise three distinguishable stress protein groups in eukaryotic cells that share a common evolutionary ancestor (11,17). The existence of hsp110 in parallel with hsp70 in the cytoplasm and of grp170 in parallel with grp78 in the ER of (apparently) all eukaryotic cells argues for important differential functions for these distantly related protein families.…”

Expression of translationally controlled tumour protein is regulated by calcium at both the transcriptional and post-transcriptional level

“…Six of these up-regulated proteins were unequivocally identified on the basis of amino acid sequence data obtained from tryptic peptides eluted from the relevant gel spot ( Table 1). Five of these [170 kDa GRP, endoplasmin, BiP, calreticulin, endoplasmic reticulum protein 5 (ERP5)], correspond to proteins whose status as ERresident molecular chaperones has been described [8,[26][27][28]. A further protein (spot 7, Figure 2), induced in response to NSP4 * Numbers refer to protein spots identified in Figure 2.…”