title: A point mutation at the ATP-binding site of the EGF-receptor abolishes signal transduction.
abstract: The EGF-receptor (EGF-R) is a transmembrane glycoprotein with intrinsic protein tyrosine kinase (TK) activity. To explore the importance of the receptor TK in the action of EGF, we have used transfected NIH-3T3 cells expressing either the normal human EGF-R or a receptor mutated at Lys721, a key residue in the presumed ATP-binding region. The wild-type receptor responds to EGF by causing inositol phosphate formation, Ca2+ influx, activation of Na+/H+ exchange and DNA synthesis. In contrast, the TK-deficient mutant receptor fails to evoke any of these responses. It is concluded that activation of the receptor TK is a crucial signal that initiates the multiple post-receptor effects of EGF leading to DNA synthesis. Furthermore, the results suggest that tyrosine phosphorylation plays a role in the activation of the phosphoinositide signalling system.
authors.affiliation: Hubrecht Laboratory, Utrecht, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Moolenaar
authors.forename: A J
authors.initials: AJ
authors.lastname: Bierman
authors.forename: B C
authors.initials: BC
authors.lastname: Tilly
authors.forename: I
authors.initials: I
authors.lastname: Verlaan
authors.forename: L H
authors.initials: LH
authors.lastname: Defize
authors.forename: A M
authors.initials: AM
authors.lastname: Honegger
authors.forename: A
authors.initials: A
authors.lastname: Ullrich
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D004247:DNA; D011505:Protein-Tyrosine Kinases; D002118:Calcium