Disease relevance of Tra1

• Expression of the 100-kda glucose-regulated protein (GRP100/endoplasmin) is associated with tumorigenicity in a model of rat colon adenocarcinoma [1].
• Because BiP and endoplasmin are known to be ER resident proteins, and because all three belong to a chaperone protein family, accumulation of these proteins in the rdw thyroid suggests that protein folding and secreting disorders underlie the hypothyroidism of the rdw rat [2].
• Using SPR spectroscopy, we studied the interaction of native glycosylated Grp94 at neutral pH and 25 and 37 degrees C with the viral immunogenic octapeptide RGYVYQGL (VSV8), derived from vesicular stomatitis virus nucleoprotein (52-59) [3].

High impact information on Tra1

• The 94-kDa glucose-regulated protein (endoplasmin, grp94) is an abundant member of the 90-kDa molecular chaperone family in the endoplasmic reticulum [4].
• At the intestinal level, associated Grp94 and BSDL were detected on microvilli and in the endosomal compartment of enterocytes [5].
• Grp94 and BSDL remain associated from leaving the pancreas until arriving at the intestinal lumen [5].
• In previous studies on the AR4-2J cell line, we have shown that secretion of bile salt-dependent lipase (BSDL) involves a multiprotein complex, including a protein of 94 kDa (p94) that is immunologically related to the chaperone Grp94, which seems to play essential roles in the folding process of BSDL [5].
• Geldanamycin (GA), which alters Grp94 functions, also affects the release of BSDL into the culture medium of AR4-2J cells [6].

Biological context of Tra1

• The phosphorylation of p210/endoplasmin by protein kinase CK2 and its coelution gives support to the involvement of this protein kinase in membrane-associated processes [7].
• At the same time, GSNO downregulated the expression of the antiapoptotic gene Sarco/endoplasmic reticulum calcium-ATPase (SERCA2b) in parallel with the downregulation of the antiapoptotic ER chaperones-glucose-regulated protein genes (Grp78 and Grp94) [8].
• Heavy chain binding protein (BiP/GRP78) and endoplasmin are exported from the endoplasmic reticulum in rat exocrine pancreatic cells, similar to protein disulfide-isomerase [9].

Anatomical context of Tra1

• During its route towards secretion, BSDL is associated with intracellular membranes by means of a multiprotein folding complex, which includes the glucose-regulated protein of 94 kDa (Grp94) [6].
• Substrates for protein kinase CK2 in insulin receptor preparations from rat liver membranes: identification of a 210-kDa protein substrate as the dimeric form of endoplasmin [7].
• Postembedding protein A-immunogold electron microscopy revealed that endoplasmin was exported from the ER and secreted to the extracellular space [9].
• Immunoblot analysis using these two antibodies showed that BiP and endoplasmin exist in both the plasma membrane and the microsomal fractions, similar to the intracellular distribution of PDI in rat exocrine pancreas [9].
• In liver and kidney of vanadium-treated rats, Grp94 was over-expressed by 50% and 150% respectively whereas no change was found in testis [10].

Associations of Tra1 with chemical compounds

• The depletion of Ca2+ stores in normal rat kidney (NRK) cells by TG abolished the retention of the KDEL-containing, Ca2+-binding, luminal ER chaperones GRP94/endoplasmin and GRP78/BiP, and resulted in the appearance of the proteins in the culture medium before inducing their synthesis [11].
• Evidence that endoplasmin expression varied inversely with serum calcium concentration, and that the inositol trisphosphate receptor also was highly expressed during maturation, supported the novel hypothesis that non-mitochondrial calcium stores play a major role in transcellular calcium transport [12].

Enzymatic interactions of Tra1

• GRP94 (endoplasmin) co-purifies with and is phosphorylated by Golgi apparatus casein kinase [13].

Other interactions of Tra1

• In vitro kinase reactions using recombinant proteins confirmed that Akt phosphorylates Hsp70, Hsp90alpha and beta, Grp94, and PDI [14].
• Together, calreticulin and endoplasmin constituted an exceptionally high proportion (5%) of soluble protein during maturation, which gives an inferred calcium capacity 67-fold higher than that of the principal cytosolic calcium-binding protein [12].

Analytical, diagnostic and therapeutic context of Tra1

• However, phosphorylation of immunoprecipitated grp94/endoplasmin was enhanced by its preincubation with purified CK2 prior to immunoprecipitation, what confirms the easy reassociation between these proteins [15].

References