Cell
Volume 40, Issue 4, April 1985, Pages 747-758
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Article
The human insulin receptor cDNA: The structural basis for hormone-activated transmembrane signalling

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Abstract

A cloned ∼5 kb cDNA (human placenta) contains the coding sequences for the insulin receptor. The nucleotide sequence predicts a 1382 amino acid precursor. The α subunit comprises the N-terminal portion of the precursor and contains a striking cysteine-rich “cross-linking” domain. The β-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 α subunit and several regions of the β 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.

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