*nlm.life
			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.

			Author Information
			(1) Institute for Cancer Research and Treatment
			(IRCC), University of Torino Medical School,
			Str. Prov. 142, Km 3.95, 10060 Candiolo,
			Italy.

			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]

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