PMID- 10438732
OWN - NLM
STAT- MEDLINE
DCOM- 19990907
LR  - 20071114
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 4
DP  - 1999 Aug 15
TI  - Proteolytic processing of big endothelin-3 by the kell blood group protein.
PG  - 1440-50
AB  - Kell blood group protein shares a consensus sequence (H.E.X.X.H) with a large
      family of zinc-dependent endopeptidases. Kell has closest homology with neutral
      endopeptidase 24.11, endothelin converting enzyme-1 (ECE-1), and the PEX gene
      product that, as a group, comprise the M13 subfamily of mammalian neutral
      endopeptidases. The proteolytic activity of the M13 members, but not of Kell, has
      been previously demonstrated. A secreted form of wild-type Kell protein (s-Kell),
      devoid of the intracellular and transmembrane domains, was expressed in sf9
      cells. As a negative control, an inactive mutant Kell protein (E582G) was
      expressed. As determined by N-terminal amino acid sequencing and mass
      spectrometry of the cleaved products, wild-type s-Kell, but not the control
      mutant protein, specifically cleaved big endothelin-3 (ET-3) at Trp(21)-Ile(22), 
      yielding ET-3, and, to a much lesser extent, also cleaved big ET-1 and big ET-2
      at Trp(21)-Val(22), yielding ET-1 and ET-2. Enzymatic activity was partially
      inhibited by phosphoramidon. s-Kell has an acidic pH optimum (pH 6.0 to 6.5).
      Like the recombinant protein, red blood cells of common Kell phenotype also
      preferentially process big ET-3, in contrast to Ko (null) cells that do not.
      These data demonstrate that the Kell blood group protein is a proteolytic enzyme 
      that processes big ET-3, generating ET-3, a potent bioactive peptide with
      multiple biological roles.
FAU - Lee, S
AU  - Lee S
AD  - The Lindsley F. Kimball Research Institute of the New York Blood Center, New
      York, NY, USA. slee@nybc.org
FAU - Lin, M
AU  - Lin M
FAU - Mele, A
AU  - Mele A
FAU - Cao, Y
AU  - Cao Y
FAU - Farmar, J
AU  - Farmar J
FAU - Russo, D
AU  - Russo D
FAU - Redman, C
AU  - Redman C
LA  - eng
GR  - HL54459/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Endothelin-3)
RN  - 0 (Kell Blood-Group System)
SB  - AIM
SB  - IM
MH  - Endothelin-3/*metabolism
MH  - Humans
MH  - Kell Blood-Group System/genetics/*metabolism
MH  - Mutation
MH  - Substrate Specificity
MH  - Transfection
EDAT- 1999/08/10 00:00
MHDA- 1999/08/10 00:01
CRDT- 1999/08/10 00:00
PHST- 1999/08/10 00:00 [pubmed]
PHST- 1999/08/10 00:01 [medline]
PHST- 1999/08/10 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Aug 15;94(4):1440-50.