: The insulin receptor (IR) gene undergoes differential splicing generating two IR isoforms, IR-A and IR-B. The roles of IR-A in cancer and of IR-B in metabolic regulation are well known but the molecular mechanisms responsible for their different biological effects are poorly understood. We aimed to identify different or similar protein substrates and signaling linked to each IR isoforms. We employed mouse fibroblasts lacking IGF1R gene and expressing exclusively either IR-A or IR-B. By proteomic analysis a total of 2530 proteins were identified and quantified. Proteins and pathways mostly associated with insulin-activated IR-A were involved in cancer, stemness and interferon signaling. Instead, proteins and pathways associated with insulin-stimulated IR-B-expressing cells were mostly involved in metabolic or tumor suppressive functions. These results show that IR-A and IR-B recruit partially different multiprotein complexes in response to insulin, suggesting partially different functions of IR isoforms in physiology and in disease.

Comparative proteomic analysis of insulin receptor isoform A and B signaling

Malaguarnera, Roberta;Giuliano, Marika;Vella, Veronica;Massimino, Michele;Vigneri, Paolo;Belfiore, Antonino
2022-01-01

Abstract

: The insulin receptor (IR) gene undergoes differential splicing generating two IR isoforms, IR-A and IR-B. The roles of IR-A in cancer and of IR-B in metabolic regulation are well known but the molecular mechanisms responsible for their different biological effects are poorly understood. We aimed to identify different or similar protein substrates and signaling linked to each IR isoforms. We employed mouse fibroblasts lacking IGF1R gene and expressing exclusively either IR-A or IR-B. By proteomic analysis a total of 2530 proteins were identified and quantified. Proteins and pathways mostly associated with insulin-activated IR-A were involved in cancer, stemness and interferon signaling. Instead, proteins and pathways associated with insulin-stimulated IR-B-expressing cells were mostly involved in metabolic or tumor suppressive functions. These results show that IR-A and IR-B recruit partially different multiprotein complexes in response to insulin, suggesting partially different functions of IR isoforms in physiology and in disease.
Cancer
Insulin
Insulin receptor isoforms
Insulin receptor signaling
Insulin receptor substrates
Quantitative proteomics
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/545524
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact