Insulin-like Growth Factor-I Receptor Signal Transduction and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) Pathway

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Abstract

The insulin-like growth factor IGF-I is an important fetal and post-natal growth factor which is also involved in tissue homeostasis via regulation of proliferation, differentiation and cell survival. In order to understand the role of IGF-I in the pathophysiology of a variety of disorders, including growth disorders, cancer and neurodegenerative diseases, a detailed knowledge of IGF-I signal transduction is required. This knowledge may also contribute to the development of new therapies directed at the IGF-I receptor or other signaling molecules. In this review, we will address IGF-I receptor signaling through the JAK/STAT pathway in IGF-I signaling and the role of cytokine-induced inhibitors of signaling (CIS) and suppressors of cytokine signaling (SOCS). It appears that, in addition to the canonical IGF-I signaling pathways through extracellular-regulated kinase (ERK) and phosphatidylinositol-3 kinase (PI3K)-Akt, IGF-I also signals through the JAK/STAT pathway. Activation of this pathway may lead to induction of SOCS molecules, well-known feedback inhibitors of the JAK/STAT pathway which also suppress of IGF-I-induced JAK/STAT signaling. Furthermore, other IGF-I-induced signaling pathways may also be modulated by SOCS. It is conceivable that the effect of these classical inhibitors of cytokine signaling directly affect IGF-I receptor signaling, because they are able to associate to the intracellular part of the IGF-I receptor. These observations indicate that CIS and SOCS molecules are key to cross-talk between IGF-I receptor signaling and signaling through receptors belonging to the hematopoietic/cytokine receptor superfamily. Theoretically, dysregulation of CIS or SOCS may affect IGF-I-mediated effects on body growth, cell differentiation, proliferation and cell survival.
Original languageEnglish
Pages (from-to)76-81
Number of pages6
JournalBiofactors
Volume35
Issue number1
Publication statusPublished - 2009

Keywords

  • IGF-I
  • signalling
  • JAK
  • STAT
  • SOCS

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