Differential activation of ErbB receptors in the rat olfactory mucosa by transforming growth factor-? and epidermal growth factorin vivo
✍ Scribed by Ezeh, Patrick I. ;Farbman, Albert I.
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 300 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0022-3034
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✦ Synopsis
Transforming growth factor-␣ (TGF-␣) and epidermal growth factor (EGF) are members of the EGF family of growth factors. They have a common receptor, the EGF receptor. This belongs to the tyrosine kinase group of receptors called the ErbB receptor family. Other members are ErbB-2, ErbB-3, and ErbB-4. Binding of either ligand to the receptor elicits an increase in tyrosine kinase activity, resulting in the autophosphorylation of the receptor followed by a phosphorylation cascade of other tyrosine kinase substrates including mitogen-activated protein kinase (MAPK). TGF-␣ and EGF have been shown to stimulate cell division in the olfactory epithelium in vitro and may regulate cell division in vivo. To investigate whether exogenous TGF-␣ or EGF has a functional effect on the olfactory mucosa in vivo, 12.5-50 g of each growth factor was administered to rats via the carotid artery. After 2 min, olfactory mucosa and liver samples were collected, homogenized, and immunoprecipitated with antibodies to the ErbB receptors. The immunoprecipitates were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting. Using phosphotyrosine antibody, the receptors were probed for phosphorylation. Activation of MAPK was also investigated using MAPK antibody. Exogenous TGF-␣ activated EGFR, ErbB-2 and MAPK, whereas EGF activated only the EGFR. TGF-␣ was a more potent activator of EGFR than EGF. Neither ligand had an effect on ErbB-3 and ErbB-4 receptors. These effects were absent in the control animals which received the same solution without the growth factor. These results are consistent with the notion that binding of TGF-␣ to EGFR may play a role in olfactory cell division in vivo.