PMID- 10037747
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 10
DP  - 1999 Mar 5
TI  - Cellular localization and role of prohormone convertases in the processing of
      pro-melanin concentrating hormone in mammals.
PG  - 6536-45
AB  - Melanin concentrating hormone (MCH) and neuropeptide EI (NEI) are two peptides
      produced from the same precursor in mammals, by cleavage at the Arg145-Arg146
      site and the Lys129-Arg130 site, respectively. We performed co-localization
      studies to reveal simultaneously the expression of MCH mRNA and proconvertases
      (PCs) such as PC1/3 or PC2. In the rat hypothalamus, PC2 was present in all MCH
      neurons, and PC1/3 was present in about 15-20% of these cells. PC1/3 or PC2 was
      not found in MCH-positive cells in the spleen. In GH4C1 cells co-infected with
      vaccinia virus (VV):pro-MCH along with VV:furin, PACE4, PC1/3, PC2, PC5/6A,
      PC5/6B, or PC7, we observed only efficient cleavage at the Arg145-Arg146 site to 
      generate mature MCH. Co-expression of pro-MCH together with PC2 and 7B2 resulted 
      in very weak processing to NEI. Comparison of pro-MCH processing patterns in
      PC1/3- or PC2-transfected PC12 cells showed that PC2 but not PC1/3 generated NEI.
      Finally, we analyzed the pattern of pro-MCH processing in PC2 null mice. In the
      brain of homozygotic mutants, the production of mature NEI was dramatically
      reduced. In contrast, MCH content was increased in the hypothalamus of PC2 null
      mice. In the spleen, a single large MCH-containing peptide was identified in both
      wild type and PC2 null mice. Together, our data suggest that pro-MCH is processed
      differently in the brain and in peripheral organs of mammals. PC2 is the key
      enzyme that produces NEI, whereas several PCs may cleave at the Arg145-Arg146
      site to generate MCH in neuronal cell types.
FAU - Viale, A
AU  - Viale A
AD  - Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UPR411, 660 route des
      Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
FAU - Ortola, C
AU  - Ortola C
FAU - Hervieu, G
AU  - Hervieu G
FAU - Furuta, M
AU  - Furuta M
FAU - Barbero, P
AU  - Barbero P
FAU - Steiner, D F
AU  - Steiner DF
FAU - Seidah, N G
AU  - Seidah NG
FAU - Nahon, J L
AU  - Nahon JL
LA  - eng
GR  - DK 13914/DK/NIDDK NIH HHS/United States
GR  - DK 20595/DK/NIDDK 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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Hypothalamic Hormones)
RN  - 0 (Melanins)
RN  - 0 (Oligopeptides)
RN  - 0 (Pituitary Hormones)
RN  - 0 (Protein Precursors)
RN  - 0 (neuropeptide EI)
RN  - 125805-24-5 (melanin-concentrating hormone precursors)
RN  - 67382-96-1 (melanin-concentrating hormone)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Hypothalamic Hormones/*metabolism
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Melanins/*metabolism
MH  - Molecular Sequence Data
MH  - Oligopeptides/*metabolism
MH  - Organ Specificity
MH  - Pituitary Hormones/*metabolism
MH  - Protein Precursors/*metabolism
MH  - Protein Processing, Post-Translational
MH  - Rats
MH  - Rats, Wistar
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - 10.1074/jbc.274.10.6536 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 5;274(10):6536-45. doi: 10.1074/jbc.274.10.6536.