Disease relevance of lysyl-aspartyl-glutamyl-leucine

• An alfalfa mosaic virus untranslated leader sequence and Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum retention signal were linked at the N and C terminus of the heavy chain, respectively. mAbP was as effective at neutralizing the activity of the rabies virus as the mammalian-derived antibody (mAbM) or human rabies Ig (HRIG) [1].
• Introduction of an ER retrieval signal, a C-terminal KDEL sequence, into the A-chain increased the toxicity and resulted in more efficient glycosylation, indicating enhanced transport from Golgi to ER [2].
• An Escherichia coli expression system was used to produce recombinant ricin A chain (RTA) and RTA modified either by the addition of a carboxyl-terminal endoplasmic reticulum retrieval sequence Lys-Asp-Glu-Leu (RTAKDEL) or a nonfunctional analogue Lys-Asp-Glu-Ala (RTAKDEA) [3].

High impact information on lysyl-aspartyl-glutamyl-leucine

• The KDEL sequence that retains soluble proteins in the endoplasmic reticulum and the mannose 6-phosphate group of lysosomal enzymes are well-characterized examples of targeting signals; other signals are less well understood [4].
• Calreticulin is a calcium storage protein and carries a COOH-terminal KDEL sequence, known to act as a retention signal for proteins destined to the lumen of the endoplasmic reticulum [5].
• Retention of these resident proteins in the ER is dependent on a carboxy-terminal signal, which in animal cells is usually Lys-Asp-Glu-Leu (KDEL) [6].
• Transport of an external Lys-Asp-Glu-Leu (KDEL) protein from the plasma membrane to the endoplasmic reticulum: studies with cholera toxin in Vero cells [7].
• By contrast, when retained by the KDEL sequence, cathepsin D is stable in the ER, indicating that retention is not sufficient to cause degradation [8].

Biological context of lysyl-aspartyl-glutamyl-leucine

• To evaluate whether E5 accumulation in the Golgi was requisite for receptor phosphorylation and cell transformation, we sequestered the E5 protein in the endoplasmic reticulum (ER)/cis Golgi by appending the ER retention KDEL sequence to its C-terminus [9].
• Previous characterization of cDNA clones for the beta-subunit of prolyl 4-hydroxylase has indicated that its C terminus has the amino acid sequence Lys-Asp-Glu-Leu, which, it has been suggested, is necessary for the retention of a polypeptide within the lumen of the endoplasmic reticulum [10].
• The polypeptide encoded by a clone designated B2 consisted of 512 amino acids and was characterized by a 24-amino acid hydrophobic leader sequence, two regions with absolute identity to the vertebrate PDI active site (Ala-Pro-Trp-Cys-Gly-His-Cys-Lys), and a C-terminal endoplasmic reticulum retention signal (Lys-Asp-Glu-Leu) [11].
• We have blocked CXCR4 function in CT-26 colon carcinoma cells by transfection of SDF-1, extended with a KDEL sequence [12].
• B-fragment with a nonfunctional KDEL sequence (B-Glyc-KDELGL) was glycosylated with about the same kinetics as B-Glyc-KDEL but localized at steady state to the Golgi apparatus [13].

Anatomical context of lysyl-aspartyl-glutamyl-leucine

• These results suggest that PDI exported from the ER to the plasma membranes in rat exocrine pancreatic cells possesses the KDEL sequence [14].
• These results indicate that the added KDEL sequence facilitated RTA entry into the cytosol [3].
• To further investigate the nature of the KDEL retention signal, oligonucleotide-directed mutagenesis and transfection was used to generate stable mouse anterior pituitary AtT-20 cell lines expressing pro-NPY mutants with variants of the KDEL sequence added to their direct carboxyl terminus [15].
• A combination of the results from analyses for transformed Arabidopsis and tobacco (Nicotiana tabacum) cells indicated that wild-type SH-EP is packed into KV-like vesicles through the KDEL sequence and is transported to vacuoles in the cells of transformants [16].
• The significance of a C-terminal tetrapeptide, Lys-Asp-Glu-Leu (KDEL), as a retention signal for the endoplasmatic reticulum was studied using cystatin C, a general thiol protease inhibitor, as the reporter protein [17].

Associations of lysyl-aspartyl-glutamyl-leucine with other chemical compounds

• On the contrary, the C-terminal KDEL sequence was demonstrated not to be essential for auxin binding, interaction with the plasma membrane, or activation of the transduction cascade although it does appear to be involved in the stability of ABP1 [18].
• In this study, we observed that exogenous peptides that were artificially fused with an endoplasmic reticulum (ER) retrieval signal, a C-terminal Lys-Asp-Glu-Leu sequence, could be efficiently presented by intracellular MHC class I molecules in a TAP- and proteasome-independent, but brefeldin A-sensitive manner [19].

Gene context of lysyl-aspartyl-glutamyl-leucine

• Total blockage of Epo secretion induced by the endoplasmic reticulum-retention amino acids Lys-Asp-Glu-Leu (KDEL) signals in 11 lines prevented autonomous proliferation, whereas a leaky retention system, observed in 3 other lines, resulted in limited autocrine stimulation without true long-term autonomous proliferation [20].
• Calnexin (Cnx), a type-1 integral transmembrane ER protein which is partially homologous to Crt but lacks the KDEL sequence, is not detected on the cell surface either [21].
• The surface GRP78 contains the KDEL sequence [21].
• Surprisingly, IL-6 carrying a COOH-terminal extension of the amino acids Lys-Asp-Glu-Leu (KDEL) was not completely retained in the endoplasmic reticulum (ER) [22].
• GFP-CRT, and GFP, with an ER signal peptide and a KDEL sequence (ER-GFP), were localised to the ER [23].

Analytical, diagnostic and therapeutic context of lysyl-aspartyl-glutamyl-leucine

• We report in this communication that the KDEL sequence when appended to the carboxy terminus of a cell surface membrane protein, dipeptidyl peptidase IV (DPPIV), resulted in its retention in the endoplasmic reticulum of transfected Madin-Darby canine kidney cells as assessed by indirect immunofluorescence [24].
• Moreover, cholera toxin, which contains a KDEL sequence, was observed by immunofluorescence microscopy to enter the endoplasmic reticulum of Vero cells in the presence of CBM [25].

References