The INSR/IGF1R receptor family

Rive Sarfstein, Haim Werner*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

6 Scopus citations


The insulin/insulin-like growth factors (IGFs) constitute a network of ligands, cell-surface receptors, and binding proteins involved in the regulation of multiple physiological and pathological processes, including metabolic, nutritional, growth, and aging events. Although the insulin receptor (INSR) and IGF1 receptor (IGF1R) share the vast majority of their downstream cytoplasmic mediators, most evidence is consistent with the notion that INSR activation (mainly by insulin) leads primarily to metabolic activities, whereas IGF1R activation (mainly by IGF1 or IGF2) leads to proliferative and differentiative events. INSR/IGF1R receptors display a remarkable similarity in genomic organization. Thus, 12 exons of the IGF1R gene are identical in size with the homologous exons of INSR, the main difference being that the IGF1R gene does not contain an equivalent of the alternatively spliced INSR exon 11. This splicing event leads to the generation of two isoforms, INSR-A and INSR-B, which lack or contain, respectively, exon 11. Overexpression of the IGF1R constitutes a typical hallmark of most types of cancer. The IGF1R exhibits a potent anti-apoptotic activity which confers upon IGF1R-expressing cells enhanced survivability, a key hallmark of cancer cells. The IGF1R emerged in recent years as a promising therapeutic target in cancer. Likewise, INSR-A seems to play an important role in proliferation and recent studies have established a role for this specific isoform in breast cancer etiology. The recognition that the INSR-A isoform is an important player in breast cancer might imply that dual (i.e., INSR and IGF1R) targeted therapy offers advantages over single receptor targeting.

Original languageEnglish
Title of host publicationReceptor Tyrosine Kinases
Subtitle of host publicationFamily and Subfamilies
PublisherSpringer International Publishing
Number of pages24
ISBN (Electronic)9783319118888
ISBN (Print)9783319118871
StatePublished - 1 Jan 2015


  • IGF1 receptor
  • IGF2
  • Insulin
  • Insulin receptor
  • Insulin-like growth factor-1 (IGF1)


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