PMID- 9488442
OWN - NLM
STAT- MEDLINE
DCOM- 19980319
LR  - 20240409
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 18
IP  - 3
DP  - 1998 Mar
TI  - NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a 
      partial agonist in vivo.
PG  - 1275-83
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen, motogen, 
      and morphogen for epithelial cells expressing its tyrosine kinase receptor, the 
      c-met proto-oncogene product, and is required for normal development in the 
      mouse. Inappropriate stimulation of Met signal transduction induces aberrant 
      morphogenesis and oncogenesis in mice and has been implicated in human cancer. 
      NK1 is a naturally occurring HGF/SF splice variant composed of only the amino 
      terminus and first kringle domain. While the biological activities of NK1 have 
      been controversial, in vitro data suggest that it may have therapeutic value as 
      an HGF/SF antagonist. Here, we directly test this hypothesis in vivo by 
      expressing mouse NK1 in transgenic mice and comparing the consequent effects with 
      those observed for mice carrying an HGF/SF transgene. Despite robust expression, 
      NK1 did not behave as an HGF/SF antagonist in vivo. Instead, NK1-transgenic mice 
      displayed most of the phenotypic characteristics associated with 
      HGF/SF-transgenic mice, including enlarged livers, ectopic skeletal-muscle 
      formation, progressive renal disease, aberrant pigment cell localization, 
      precocious mammary lobuloalveolar development, and the appearance of mammary, 
      hepatocellular, and melanocytic tumors. And like HGF/SF-transgenic livers, NK1 
      livers had higher levels of tyrosine-phosphorylated complexes associated with 
      Met, suggesting that the mechanistic basis for the effects of NK1 overexpression 
      in vivo was autocrine activation of Met. We conclude that NK1 acts in vivo as a 
      partial agonist. As such, the efficacy of NK1 as a therapeutic HGF/SF antagonist 
      must be seriously questioned.
FAU - Jakubczak, J L
AU  - Jakubczak JL
AD  - Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 
      20892, USA.
FAU - LaRochelle, W J
AU  - LaRochelle WJ
FAU - Merlino, G
AU  - Merlino G
LA  - eng
SI  - GENBANK/AF042856
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA, Complementary)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - *Alternative Splicing
MH  - Animals
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Gene Expression
MH  - Hepatocyte Growth Factor/*agonists/biosynthesis/genetics
MH  - Humans
MH  - Kidney/growth & development
MH  - Liver/growth & development
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Neoplasms/etiology
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-met/metabolism
PMC - PMC108840
EDAT- 1998/03/06 00:00
MHDA- 1998/03/06 00:01
PMCR- 1998/03/01
CRDT- 1998/03/06 00:00
PHST- 1998/03/06 00:00 [pubmed]
PHST- 1998/03/06 00:01 [medline]
PHST- 1998/03/06 00:00 [entrez]
PHST- 1998/03/01 00:00 [pmc-release]
AID - 1439 [pii]
AID - 10.1128/MCB.18.3.1275 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1998 Mar;18(3):1275-83. doi: 10.1128/MCB.18.3.1275.