PMID- 11502202
OWN - NLM
STAT- MEDLINE
DCOM- 20010920
LR  - 20211203
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 268
IP  - 16
DP  - 2001 Aug
TI  - Hepatocyte growth factor/scatter factor stimulates migration of rat mammary 
      fibroblasts through both mitogen-activated protein kinase and 
      phosphatidylinositol 3-kinase/Akt pathways.
PG  - 4423-9
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is considered to be a 
      mesenchymal-derived factor that acts via a dual system receptor, consisting of 
      the MET receptor and proteoglycans present on adjacent epithelial cells. 
      Surprisingly, HGS/SF stimulated the migration of rat mammary (Rama) 27 
      fibroblasts, although it failed to stimulate their proliferation. HGF/SF 
      stimulated a transient activation of mitogen-activated protein kinases p44 and 
      p42 (p42/44(MAPK)), with a maximum level of dual phosphorylation of p42/44(MAPK) 
      occurring 10-15 min after the addition of the growth factor, which was followed 
      by a rapid decrease to near basal levels after 20 min. Interestingly, a second 
      phase of p42/44(MAPK) dual phosphorylation was observed at later times (3 h to 10 
      h). PD098059, a specific inhibitor of MEK-1, prevented the dual phosphorylation 
      of p42/44(MAPK) and also the phosphorylation of p90(RSK) (ribosomal subunit S6 
      kinase), which mirrored the kinetics of p42/44(MAPK) phosphorylation. Moreover, 
      PD098059 prevented the HGF/SF-induced migration of Rama 27 cells. HGF/SF also 
      induced an early increase in the phosphorylation of protein kinase B/Akt. Akt 
      phosphorylation was elevated 15 min after the addition of HGF/SF and then 
      declined to basal levels by 30 min. Wortmannin, an inhibitor of 
      phosphatidylinositol 3-kinase (PtdIns3K), prevented the increase in Akt 
      phosphorylation and abolished HGF/SF-induced migration of fibroblasts. PD098059 
      also inhibited the stimulation of Akt phosphorylation by HGF/SF and wortmannin 
      similarly inhibited the stimulation of p42/44(MAPK) dual phosphorylation. These 
      results suggest that HGF/SF-induced motility depends on both the transient dual 
      phosphorylation of p42/44(MAPK) and the activation of PtdIns3K in Rama 27 
      fibroblasts and that these pathways are mutually dependent.
FAU - Delehedde, M
AU  - Delehedde M
AD  - School of Biological Sciences, University of Liverpool, UK.
FAU - Sergeant, N
AU  - Sergeant N
FAU - Lyon, M
AU  - Lyon M
FAU - Rudland, P S
AU  - Rudland PS
FAU - Fernig, D G
AU  - Fernig DG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Androstadienes)
RN  - 0 (Flavonoids)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Akt1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Fibroblasts/drug effects/physiology
MH  - Flavonoids/pharmacology
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/*physiology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphorylation
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Wortmannin
EDAT- 2001/08/15 10:00
MHDA- 2001/09/21 10:01
CRDT- 2001/08/15 10:00
PHST- 2001/08/15 10:00 [pubmed]
PHST- 2001/09/21 10:01 [medline]
PHST- 2001/08/15 10:00 [entrez]
AID - ejb2363 [pii]
AID - 10.1046/j.1432-1327.2001.02363.x [doi]
PST - ppublish
SO  - Eur J Biochem. 2001 Aug;268(16):4423-9. doi: 10.1046/j.1432-1327.2001.02363.x.