PubMed Journals: Oncogene
Source: PMID: 10734310
⇦ ⇨ Oncogene. 2000 Mar 16;19(12):1509-18.
Sustained recruitment of phospholipase C-gamma
to Gab1 is required for HGF-induced branching tubulogenesis.
Gual P(1), Giordano S, Williams TA, Rocchi
S, Van Obberghen E, Comoglio PM.
(1) Institute for Cancer Research and Treatment
(IRCC), University of Torino Medical School,
Str. Prov. 142, Km 3.95, 10060 Candiolo,
A distinctive property of Hepatocyte Growth Factor
(HGF) is its ability to induce differentiation
of tubular structures from epithelial and
endothelial cells (branching tubulogenesis).
The HGF receptor directly activates PI3
kinase, Ras and STAT signalling pathways
and phosphorylates the adaptator GRB2 Associated
Binder-1 (Gab1). Gab1 is also phosphorylated
in response to Epidermal Growth Factor
(EGF) but is unable to induce tubule formation.
Comparison of 32P-peptide maps of Gab1 from
EGF- versus HGF-treated cells, demonstrates
that the same sites are phosphorylated in
vivo. However, while both EGF and HGF induce
rapid tyrosine phosphorylation of Gab1 with
a peak at 15 min, the phosphorylation persists
for over 1 h, only in response to HGF. Nine
tyrosines are phosphorylated by both receptors.
Three of them (Y307, Y373, Y407) bind phospholipase
C-gamma (PLC-gamma). Interestingly, the
overexpression of a Gab1 mutant unable to
bind PLC-gamma (Gab1 Y307/373/407F) did
not alter HGF-stimulated cell scattering,
only partially reduced the growth stimulation
but completely abolished HGF-mediated tubulogenesis.
It is concluded that sustained recruitment
of PLCgamma to Gab1 plays an important role
in branching tubulogenesis.
DOI: 10.1038/sj.onc.1203514 PMID: 10734310
[Indexed for MEDLINE]