Differential activation of ErbB receptors in the rat olfactory mucosa by transforming growth factor-alpha and epidermal growth factor in vivo.
Transforming growth factor-alpha (TGF-alpha) 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-alpha 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-alpha or EGF has a functional effect on the olfactory mucosa in vivo, 12.5-50 micrograms 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-alpha activated EGFR, ErbB-2 and MAPK, whereas EGF activated only the EGFR. TGF-alpha 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-alpha to EGFR may play a role in olfactory cell division in vivo.
Ezeh
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Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Farbman
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D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D020893:Receptor, ErbB-3; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D016211:Transforming Growth Factor alpha