PMID- 9365521
OWN - NLM
STAT- MEDLINE
DCOM- 19971211
LR  - 20101118
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 173
IP  - 2
DP  - 1997 Nov
TI  - Differential requirement of Grb2 and PI3-kinase in HGF/SF-induced cell motility 
      and tubulogenesis.
PG  - 196-201
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine 
      that induces mitogenesis, motility, invasion, and morphogenesis of several 
      epithelial and endothelial cell lines in culture. The receptor for HGF/SF has 
      been identified as the Met tyrosine kinase. To investigate the signaling pathways 
      that are involved in these events, we have generated chimeric receptors 
      containing the extracellular domain of the colony stimulating factor-1 (CSF-1) 
      receptor fused to the transmembrane and intracellular domains of the Met receptor 
      (MET). Madin-Darby canine kidney (MDCK) epithelial cells, expressing the CSF-MET 
      chimera dissociate, scatter and form branching tubules in response to CSF-1. 
      However, cells expressing a mutant CSF-MET receptor containing a phenylalanine 
      substitution for tyrosine 1356 (Y1356F) are unable to scatter or form branching 
      tubules following stimulation with CSF-1. Tyrosine 1356 is essential for the 
      recruitment of multiple substrates including Grb2, the p85 subunit of PI3-kinase, 
      and PLC gamma. To investigate the role of these signaling pathways, we have 
      generated a mutant receptor that selectively fails to associate with Grb2, and 
      have treated MDCK cells with potent inhibitors of PLC gamma, PI3-kinase, and 
      p70S6K, a downstream target of PI3-kinase. Our results implicate pathways 
      downstream from PI3-kinase in cell dissociation and scatter, whereas pathways 
      downstream from Grb2 are required for branching tubulogenesis in MDCK cells.
FAU - Royal, I
AU  - Royal I
AD  - Royal Victoria Hospital, Department of Medicine, McGill University, Montreal, 
      Quebec, Canada.
FAU - Fournier, T M
AU  - Fournier TM
FAU - Park, M
AU  - Park M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Colony-Stimulating Factors)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Colony-Stimulating Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Cell Movement/physiology
MH  - Chimera/genetics
MH  - Colony-Stimulating Factors/pharmacology
MH  - Dogs
MH  - GRB2 Adaptor Protein
MH  - Hepatocyte Growth Factor/*physiology
MH  - Kidney/*cytology/drug effects/*physiology
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Proteins/metabolism/*physiology
MH  - Proto-Oncogene Proteins c-met/genetics
MH  - Receptors, Colony-Stimulating Factor/genetics
MH  - Tight Junctions/metabolism
EDAT- 1997/11/20 07:03
MHDA- 2000/06/20 09:00
CRDT- 1997/11/20 07:03
PHST- 1997/11/20 07:03 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1997/11/20 07:03 [entrez]
AID - 10.1002/(SICI)1097-4652(199711)173:2<196::AID-JCP20>3.0.CO;2-D [pii]
AID - 10.1002/(SICI)1097-4652(199711)173:2<196::AID-JCP20>3.0.CO;2-D [doi]
PST - ppublish
SO  - J Cell Physiol. 1997 Nov;173(2):196-201. doi: 
      10.1002/(SICI)1097-4652(199711)173:2<196::AID-JCP20>3.0.CO;2-D.