PMID- 9786910
OWN - NLM
STAT- MEDLINE
DCOM- 19981201
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 44
DP  - 1998 Oct 30
TI  - The carboxyl-terminal tail of kinase splitting membranal proteinase/meprin beta 
      is involved in its intracellular trafficking.
PG  - 29043-51
AB  - The kinase splitting membranal proteinase (KSMP), was recently shown to be 
      identical with the beta-subunit of meprin. Meprin is a metalloendoproteinase 
      located in brush border membranes and composed of the two types of subunits, 
      alpha and beta. Despite their high sequence homology and similar domain 
      organization, meprin subunits are differently processed during maturation; meprin 
      alpha is retained in the endoplasmic reticulum (ER), and undergoes a proteolytic 
      removal of the transmembrane and cytoplasmic domains, prior to its export from 
      this organelle. In contrast, meprin beta retains these domains even after 
      reaching its final destination in the plasma membrane. Using truncated mutants of 
      rat meprin beta expressed in Cos-7 and human embryonic kidney (HEK) 293 cells, we 
      show here that the cytoplasmic tail is indispensable for its exit from the ER. A 
      meprin beta mutant lacking the last 25 amino acids is shown to be 
      transport-incompetent, although it does not contain any of the known ER retention 
      signals. Systematic analysis of the rate of the ER to Golgi transport using a 
      series of mutants with Ala or Pro substitutions in the tail, suggests that while 
      no specific amino acid residue by itself is imperative for normal intracellular 
      trafficking of meprin beta, the insertion of a bend at a distinct position in the 
      tail (specifically by a Y685P mutation) suffices to retain this protein in the 
      ER. We propose that the very length of the cytoplasmic tail, as well as its 
      secondary structure are essential for the ER to Golgi transport of meprin beta, 
      possibly by allowing an interaction with a cargo receptor.
FAU - Litovchick, L
AU  - Litovchick L
AD  - Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 
      76100, Israel.
FAU - Chestukhin, A
AU  - Chestukhin A
FAU - Shaltiel, S
AU  - Shaltiel S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.63 (meprin B)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - COS Cells
MH  - Cell Line
MH  - Cytoplasm/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Golgi Apparatus/metabolism
MH  - Humans
MH  - Hydrolysis
MH  - Metalloendopeptidases/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Mutagenesis
MH  - Phosphotransferases/*metabolism
MH  - Protein Folding
MH  - Rats
EDAT- 1998/10/24 00:00
MHDA- 1998/10/24 00:01
CRDT- 1998/10/24 00:00
PHST- 1998/10/24 00:00 [pubmed]
PHST- 1998/10/24 00:01 [medline]
PHST- 1998/10/24 00:00 [entrez]
AID - S0021-9258(19)59490-X [pii]
AID - 10.1074/jbc.273.44.29043 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Oct 30;273(44):29043-51. doi: 10.1074/jbc.273.44.29043.