PMID- 17079873
OWN - NLM
STAT- MEDLINE
DCOM- 20070209
LR  - 20091119
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 38
IP  - 5
DP  - 2006 Oct 31
TI  - An alternatively spliced form of Met receptor is tumorigenic.
PG  - 565-73
AB  - The Met tyrosine kinase receptor is a widely expressed molecule, which mediates 
      pleiotropic cellular responses following activation by its ligand, hepatocyte 
      growth factor/scatter factor (HGF/SF). Previously, one of the authors identified 
      an alternatively spliced form of Met (Met-SM) that lacked a single exon of a 
      47-amino-acid segment in the juxtamembrane domain. Here we report that Met-SM is 
      a potent transforming gene in NIH3T3 mouse fibroblast cells. Met-SM-transfected 
      NIH3T3 cells show stronger foci-forming activity than wild type- Met-transfected 
      ones. In addition, Met-SM-transfected NIH3T3 cells form colonies in soft agar and 
      are tumorigenic in athymic nu/nu mice. Furthermore, HGF/SF significantly 
      increases the focus-forming activity of Met-SM comparing to wild type Met. The 
      amount of protein and of tyrosine kinase activity of Met-SM accumulates to a high 
      level following HGF/SF treatment. The accumulation of Met-SM correlated well with 
      its delayed ubiquitination and increased stability. These results are consistent 
      with the important role of the juxtamembrane domain in protein stability of Met 
      receptor and suggest that the alternatively-spliced form may contribute to the 
      development and progression of human cancer.
FAU - Lee, Jae-Ho
AU  - Lee JH
AD  - Department of Biochemistry, School of Medicine, Ajou University, Suwon 443-721, 
      Korea. jhlee64@ajou.ac.kr
FAU - Gao, Chong Feng
AU  - Gao CF
FAU - Lee, Chong Chou
AU  - Lee CC
FAU - Kim, Myung Deok
AU  - Kim MD
FAU - Vande Woude, George F
AU  - Vande Woude GF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Carcinogens)
RN  - 0 (Mutant Proteins)
RN  - 0 (Protein Isoforms)
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  - Carcinogenicity Tests
MH  - Carcinogens/*metabolism
MH  - Down-Regulation
MH  - Female
MH  - Hepatocyte Growth Factor/pharmacology
MH  - Mice
MH  - Mice, Nude
MH  - Mutant Proteins/metabolism/physiology
MH  - NIH 3T3 Cells
MH  - Protein Isoforms/metabolism/physiology
MH  - Proto-Oncogene Proteins c-met/*metabolism/*physiology
EDAT- 2006/11/03 09:00
MHDA- 2007/02/10 09:00
CRDT- 2006/11/03 09:00
PHST- 2006/11/03 09:00 [pubmed]
PHST- 2007/02/10 09:00 [medline]
PHST- 2006/11/03 09:00 [entrez]
AID - 2006103013 [pii]
AID - 10.1038/emm.2006.66 [doi]
PST - ppublish
SO  - Exp Mol Med. 2006 Oct 31;38(5):565-73. doi: 10.1038/emm.2006.66.