scholarly journals Interactions of EGF, Wnt and HOM-C genes specify the P12 neuroectoblast fate in C. elegans

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2337-2347 ◽  
Author(s):  
L.I. Jiang ◽  
P.W. Sternberg
Keyword(s):  
Signaling Pathway ◽  
Growth Factor Signaling ◽  
C Elegans ◽  
Downstream Target ◽  
Epidermal Growth Factor Signaling ◽  
Epidermal Growth ◽  
Temporal And Spatial ◽  
Egf Signaling ◽  
Inductive Signal ◽  
Growth Factor Signaling Pathway

We investigate how temporal and spatial interactions between multiple intercellular and intracellular factors specify the fate of a single cell in Caenorhabditis elegans. P12, which is a ventral cord neuroectoblast, divides postembryonically to generate neurons and a unique epidermal cell. Three classes of proteins are involved in the specification of P12 fate: the LIN-3/LET-23 epidermal growth factor signaling pathway, a Wnt protein LIN-44 and its candidate receptor LIN-17, and a homeotic gene product EGL-5. We show that LIN-3 is an inductive signal sufficient to promote the P12 fate, and the conserved EGF signaling pathway is utilized for P12 fate specification; egl-5 is a downstream target of the lin-3/let-23 pathway in specifying P12 fate; and LIN-44 and LIN-17 act synergistically with lin-3 in the specification of the P12 fate. The Wnt pathway may function early in development to regulate the competence of the cells to respond to the LIN-3 inductive signal.

scholarly journals GH modulates hepatic epidermal growth factor signaling in the mouse

2009 ◽  
Vol 204 (3) ◽  
pp. 299-309 ◽  
Author(s):  
Lorena González ◽  
Ma. Eugenia Díaz ◽  
Johanna G Miquet ◽  
Ana I Sotelo ◽  
Diego Fernández ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transgenic Mice ◽  
Egf Receptor ◽  
Tyrosine Phosphatase ◽  
Growth Factor Signaling ◽  
Signaling Crosstalk ◽  
Epidermal Growth Factor Signaling ◽  
Epidermal Growth ◽  
Egf Signaling

Epidermal growth factor (EGF) is a key regulator of cell survival and proliferation involved in the pathogenesis and progression of different types of cancer. The EGF receptor (EGFR) is activated by binding of the specific ligand but also by transactivation triggered by different growth factors including GH. Chronically, elevated GH levels have been associated with the progression of hepatocellular carcinoma. Considering EGF and GH involvement in cell proliferation and their signaling crosstalk, the objective of the present study was to analyze GH modulatory effects on EGF signaling in liver. For this purpose, GH receptor-knockout (GHR-KO) and GH-overexpressing transgenic mice were used. EGFR content was significantly decreased in GHR-KO mice. Consequently, EGF-induced phosphorylation of EGFR, AKT, ERK1/2, STAT3, and STAT5 was significantly decreased in these mice. In contrast, EGFR content as well as its basal tyrosine phosphorylation was increased in transgenic mice overexpressing GH. However, EGF stimulation caused similar levels of EGFR, AKT, and ERK1/2 phosphorylation in normal and transgenic mice, while EGF induction of STAT3 and STAT5 phosphorylation was inhibited in the transgenic mice. Desensitization of the STATs was related to decreased association of these proteins to the EGFR and increased association between STAT5 and the tyrosine phosphatase SH2-containing phosphatase-2. While GHR knockout is associated with diminished expression of the EGFR and a concomitant decrease in EGF signaling, GH overexpression results in EGFR overexpression with different effects depending on the signaling pathway analyzed: AKT and ERK1/2 pathways are induced by EGF, while STAT3 and STAT5 activation is heterologously desensitized.

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