DIFFERENTIAL ACTIVATION OF ERBB RECEPTORS IN THE RAT OLFACTORY MUCOSABY TRANSFORMING GROWTH-FACTOR-ALPHA AND EPIDERMAL GROWTH-FACTOR IN-VIVO

Transforming growth factor-alpha (TGF-alpha) and epidermal growth fact or (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 ErbB2, ErbB-3, and ErbB-4, Binding of either ligand to the receptor e licits an increase in tyrosine kinase activity, resulting in the autop hosphorylation of the receptor followed by a phosphorylation cascade o f other tyrosine kinase substrates including mitogen-activated protein kinase (MAPK), TGF-alpha and EGF have been shown to stimulate cell di vision in the olfactory epithelium in vitro and may regulate cell divi sion in vivo. To investigate whether exogenous TGF-alpha or EGF has a functional effect on the olfactory mucosa in vivo, 12.5-50 mu g of eac h 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 im munoprecipitates were subjected to sodium dodecyl sulfate-polyacrylami de gel electrophoresis and Western immunoblotting, Using phosphotyrosi ne antibody, the receptors were probed for phosphorylation. Activation of MAPK was also investigated using MAPK antibody. Exogenous TGP-alph a activated EGPR, ErbB-2 and MAPK, whereas EGF activated only the EGFR , TGF-alpha was a more potent activator of EGFR than EGF, Neither liga nd had an effect on ErbB-3 and ErbB-4 receptors, These effects were ab sent in the control animals which received the same solution without t he growth factor, These results are consistent with the notion that bi nding of TGF-alpha to EGFR may play a role in olfactory cell division in vivo. (C) 1998 John Wiley & Sons.