PMID- 1618748
OWN - NLM
STAT- MEDLINE
DCOM- 19920806
LR  - 20231213
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 267
IP  - 18
DP  - 1992 Jun 25
TI  - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related 
      protein binds and internalizes Pseudomonas exotoxin A.
PG  - 12420-3
AB  - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related 
      protein (alpha 2 MR/LRP) is a large cell-surface glycoprotein consisting of a 
      515-kDa and an 85-kDa polypeptide; this receptor is thought to be responsible for 
      the binding and endocytosis of activated alpha 2-macroglobulin and apoE-enriched 
      beta-very low density lipoprotein. A similar high molecular weight glycoprotein 
      has been identified as a potential receptor for Pseudomonas exotoxin A (PE). We 
      demonstrate that the alpha 2 MR/LRP and the PE-binding glycoprotein have a 
      similar mobility upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis 
      and are immunologically indistinguishable. Furthermore, affinity-purified alpha 2 
      MR/LRP binds specifically to PE but not to a mutant toxin defective in its 
      ability to bind cells. The 39-kDa receptor-associated protein, which blocks 
      binding of ligands to alpha 2 MR/LRP, also prevents binding and subsequent 
      toxicity of PE for mouse fibroblasts. The concentration of receptor-associated 
      protein that was required to reduce binding and toxicity to 50% was approximately 
      14 nM, a value virtually identical to the KD measured for the interaction of 
      receptor-associated protein with the purified receptor. Overall, the studies 
      strongly suggest that the alpha 2 MR/LRP is responsible for internalizing PE.
FAU - Kounnas, M Z
AU  - Kounnas MZ
AD  - Biochemistry Laboratory, American Red Cross, Rockville, Maryland 20855.
FAU - Morris, R E
AU  - Morris RE
FAU - Thompson, M R
AU  - Thompson MR
FAU - FitzGerald, D J
AU  - FitzGerald DJ
FAU - Strickland, D K
AU  - Strickland DK
FAU - Saelinger, C B
AU  - Saelinger CB
LA  - eng
GR  - AI17529/AI/NIAID NIH HHS/United States
GR  - GM42581/GM/NIGMS NIH HHS/United States
GR  - HL30200/ +/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bacterial Toxins)
RN  - 0 (Exotoxins)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Virulence Factors)
RN  - EC 2.4.2.- (ADP Ribose Transferases)
SB  - IM
MH  - *ADP Ribose Transferases
MH  - Amino Acid Sequence
MH  - Animals
MH  - Bacterial Toxins/*metabolism
MH  - Cells, Cultured
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Exotoxins/*metabolism
MH  - Fibroblasts/cytology
MH  - Humans
MH  - Low Density Lipoprotein Receptor-Related Protein-1
MH  - Mice
MH  - Molecular Sequence Data
MH  - Pseudomonas aeruginosa/*metabolism
MH  - Receptors, Immunologic/*metabolism
MH  - *Virulence Factors
MH  - Pseudomonas aeruginosa Exotoxin A
EDAT- 1992/06/25 00:00
MHDA- 1992/06/25 00:01
CRDT- 1992/06/25 00:00
PHST- 1992/06/25 00:00 [pubmed]
PHST- 1992/06/25 00:01 [medline]
PHST- 1992/06/25 00:00 [entrez]
AID - S0021-9258(18)42291-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1992 Jun 25;267(18):12420-3.