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Key Points The growth hormone receptor mediates a wide range of growth-related and metabolic actions, both directly and via insulin-like growth factor 1 (IGF-1) Receptor loss-of-function, predominantly owing to mutations in the extracellular domain, results in growth hormone insensitivity or Laron syndrome Receptor gain-of-function mutations are not known, but excessive receptor stimulation by growth hormone leads to gigantism, adult acromegaly and cancer (if autocrine growth hormone signaling is involved) The hormonereceptor complex is well-defined at a molecular level for the extracellular domain The growth hormone receptor exists as a constitutive dimer, and activation involves rearrangement of the receptor subunits to align the tyrosine-protein kinases JAK2 and Src bound below the cell membrane for activation JAK2 and the Src family of proto-oncogene tyrosine-protein kinases initiate signaling, the former involving the key transcription factor signal transducer and activator of transcription 5b This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 12 print issues and online access $189.00 per year only $15.75 per issue Buy this article Purchase on SpringerLink Instant access to the full article PDF

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