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Published on: July 20, 2014
Shc is a substrate of the rat intestinal epidermal growth factor receptor tyrosine kinase
1Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Background & Aims:
Epidermal growth factor (EGF) has been shown to induce intestinal proliferation and maturation; however, little information is available regarding substrates of the intestinal EGF receptor tyrosine kinase. The purpose of this study was to determine if src homologous collagen-like protein (Shc) was an in vivo substrate of the intestinal EGF receptor.
Methods:
Ten-day-old rats were treated with EGF or were breast-fed. In some experiments, IEC-6 cells were treated with EGF. Intestinal tissue and cell fractions were studied by immunodetection to compare the tyrosine phosphorylation state and the subcellular localization of intestinal proteins.
Results:
The total tyrosine phosphorylation state of intestinal proteins was increased threefold by EGF. Tyrosine phosphorylation of the EGF receptor and Shc were rapidly increased by EGF. The association of Grb2 with Shc increased fourfold and fivefold. Plasma membrane translocation of Shc and associated phosphotyrosyl proteins was increased within 30 seconds of EGF treatment.
Conclusions:
Shc is a substrate of the intestinal EGF receptor in vivo. EGF-induced association of Shc with the adapter protein Grb2 may have implications for activation of the p21ras signaling pathway in the intestine. The EGF-induced membrane association of Shc with two other phosphotyrosyl proteins suggests involvement of Shc in additional aspects of EGF-receptor signaling in the intestine.
Insights
Src homologous collagen-like protein (Shc) is a substrate of the intestinal epidermal growth factor (EGF) receptor in vivo. EGF treatment rapidly increases Shc tyrosine phosphorylation and membrane association, suggesting its role in intestinal EGF signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gastroenterology
Background:
- Epidermal Growth Factor (EGF) promotes intestinal growth and maturation.
- The role of intestinal EGF receptor tyrosine kinase substrates is not well understood.
Purpose of the Study:
- To investigate if src homologous collagen-like protein (Shc) functions as an in vivo substrate of the intestinal EGF receptor.
Main Methods:
- Treatment of 10-day-old rats and IEC-6 cells with EGF.
- Immunodetection of intestinal tissue and cell fractions.
- Analysis of protein tyrosine phosphorylation and subcellular localization.
Main Results:
- EGF increased total protein tyrosine phosphorylation threefold.
- EGF rapidly enhanced tyrosine phosphorylation of the EGF receptor and Shc.
- Shc-Grb2 association increased significantly, with rapid plasma membrane translocation of Shc.
Conclusions:
- Shc acts as an in vivo substrate for the intestinal EGF receptor.
- EGF-induced Shc-Grb2 interaction may activate intestinal p21ras signaling.
- Shc's membrane association with other proteins indicates broader roles in intestinal EGF-receptor signaling.
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