PMID- 8886986
OWN - NLM
STAT- MEDLINE
DCOM- 19970319
LR  - 20220215
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 109 ( Pt 9)
DP  - 1996 Sep
TI  - C-Met signalling in an HGF/SF-insensitive variant MDCK cell line with 
      constitutive motile/invasive behaviour.
PG  - 2371-81
AB  - The Met protein is a receptor tyrosine kinase for hepatocyte growth 
      factor/scatter factor (HGF/SF), a multifunctional growth factor with mitogenic, 
      motogenic and morphogenic properties. A morphologically altered variant of the 
      MDCK cell line, MDCK-1, spontaneously exhibits a number of features associated 
      with a partial HGF/SF-Met induced phenotype (less adhesive colonies in culture, 
      enhanced invasion and motility, nascent tubule formation), but paradoxically does 
      not respond to HGF/SF treatment. Although the overall cell surface expression and 
      distribution of Met were found to be similar in parental MDCK cells and the 
      MDCK-1 cell line, p145met autophosphorylation (+/ HGF/SF) was significantly 
      reduced in MDCK-1 cells in vitro and in vivo when compared with parental MDCK 
      cells. In contrast, EGF induced cell proliferation and EGF receptor 
      autophosphorylation to similar levels in both cell lines. The basal levels of 
      protein tyrosine phosphorylation were higher in MDCK-1 cells when compared with 
      parental MDCK cells, including that of two prominent proteins with molecular 
      masses of approximately 185 kDa and 220 kDa. Moreover, both p185 and p220 are 
      present and tyrosine phosphorylated in Met immunoprecipitates from MDCK-1 cells 
      (+/-HGF/SF), but not parental MDCK cells. In addition, Met immunocomplexes from 
      MDCK-1 cells exhibited an approximately 3-fold increased tyrosine kinase activity 
      in vitro when compared with MDCK cells, correlating with the higher basal levels 
      of total phosphotyrosine. Treatment of MDCK-1 cells with the tyrosine kinase 
      inhibitor herbimycin A reverted the cell phenotype to a more MDCK-like morphology 
      in culture, with a concomitant reduction in the tyrosine phosphorylation 
      predominantly of p220. Taken together these data suggest that aberrations in Met 
      activity and associated signalling render MDCK-1 cells insensitive to HGF/SF, and 
      may also mediate alterations in MDCK-1 cell behaviour.
FAU - Webb, C P
AU  - Webb CP
AD  - School of Biological Sciences, University of East Anglia, Norwich, Norfolk, UK.
FAU - Lane, K
AU  - Lane K
FAU - Dawson, A P
AU  - Dawson AP
FAU - Vande Woude, G F
AU  - Vande Woude GF
FAU - Warn, R M
AU  - Warn RM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Benzoquinones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Quinones)
RN  - 1W306TDA6S (Rifabutin)
RN  - 42HK56048U (Tyrosine)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 70563-58-5 (herbimycin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Benzoquinones
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cell Size/drug effects
MH  - Dogs
MH  - Drug Resistance
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/pharmacology
MH  - Hepatocyte Growth Factor/metabolism/pharmacology
MH  - Lactams, Macrocyclic
MH  - Phenotype
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Quinones/pharmacology
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Rifabutin/analogs & derivatives
MH  - Signal Transduction
MH  - Tyrosine/metabolism
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
AID - 10.1242/jcs.109.9.2371 [doi]
PST - ppublish
SO  - J Cell Sci. 1996 Sep;109 ( Pt 9):2371-81. doi: 10.1242/jcs.109.9.2371.