Nuclear epidermal growth factor (EGF) receptor as a new site of action for EGF

Nuclear epidermal growth factor (EGF) receptor as a new site of action for EGF

122 NUCLLAR EplOERMAL GROHTH FACTOR (EGF) RECEPTOR AS A NEW SITE OF ACTIO!, FOR EGF U. Marti. DPPartnent of Clinical Pharmacology. U"i"ersity of Grme...

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122

NUCLLAR EplOERMAL GROHTH FACTOR (EGF) RECEPTOR AS A NEW SITE OF ACTIO!, FOR EGF U. Marti. DPPartnent of Clinical Pharmacology. U"i"ersity of Grme. Gerne. Swotaerland.

durrng the pre-S Phase of regeneration after partral hepaiectomy. I” rat hrer, endocytosed EGF is dIverted from Its normal degraddtive pathway and accumulates in the nuclei of hepatocytes Instead. The role of tins nuclear EGF accumulation is not clear. We further analyred th,s nuclear-associated EGF by SDS-PAGE and found part of it bound to a prote:n vrth 180 kDa w~lecu!~r weight. the molecuiar weight of the EGF receptor on the plwla membrane. Western blots with ,solated nucle, fron 8 hr regenerating and control rat Her were performed ur,ng maoclonal ant,bodiss against the cell surface EGF receptor. We were able to identrfiy a nuclear EGF receptor in both. nuclei isolated frun regrwrating and control liver. Gindrng assays wth lrolated iiuclel from regenerating and control lvvel and wolated Plasma nembranes did not resolve any rign~ficant difference in the Kd'. for EGF b,nd,ng. but nuclei frcm regenerating and control liver show cn!r about 6% and 10X. respect,ve,y. of the number of brnding srtes per "J protein found 'Inplasma membranes. We sycculate this redustron 1s due to Preoccupatio" of ths receptor by endogeneus EG:. lran~unoelectronmicroscopy of isolated nuclei with colloidal gold show a" exclusive locariar. of label over the nuclear rr.ter