PT Journal AU Ebina, Y Ellis, L Jarnagin, K Edery, M Graf, L Clauser, E Ou, JH Masiarz, F Kan, YW Goldfine, ID TI The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. SO Cell PD Apr PY 1985 BP 747 EP 758 VL 40 IS 4 LA eng DE Amino Acid Sequence; Base Sequence; Cell Membrane; Chromosomes, Human, 19-20; DNA; Female; Humans; Membrane Proteins; Nucleic Acid Hybridization; Placenta; Poly A; Pregnancy; Protein Kinases; Protein-Tyrosine Kinases; RNA, Messenger; Receptor, Epidermal Growth Factor; Receptor, Insulin; Receptors, Cell Surface; Structure-Activity Relationship; Transcription, Genetic AB A cloned approximately 5 kb cDNA (human placenta) contains the coding sequences for the insulin receptor. The nucleotide sequence predicts a 1382 amino acid precursor. The alpha subunit comprises the N-terminal portion of the precursor and contains a striking cysteine-rich "cross-linking" domain. The beta-subunit (the C-terminal portion of the precursor) contains a transmembrane domain and, in the intracellular region, the elements of a tyrosine phosphokinase: an ATP-binding site and a possible tyrosine autophosphorylation site or sites. The overall structure is reminiscent of the EGF receptor; the cross-linking domain of the alpha subunit and several regions of the beta subunit exhibit sequence homology with the EGF receptor. The phosphokinase domain also exhibits homology with some oncogenic proteins that have tyrosine phosphokinase activity, in particular, a striking homology with v-ros. Southern blotting experiments suggest that the coding region spans more than 45 kb. The insulin receptor gene is located on chromosome 19. ER