PDK (PDPK1), insulin, IRS-4, MNK2(GPRK7), IGF-1, IRS-1, p70 S6 kinase2, SOS, HIF-1, tuberin, Grb2, PI3K cat class IA, H-Ras, 126.96.36.199, MEK1(MAP2K1), IBP3, p70 S6 kinase1, 4E-BP1, VEGF-A, IGF-1 receptor, PI3K reg class IA, Shc, IRS-2, RPS6, RHEB2, eIF4E, c-Raf-1, PKC-zeta, PI(4,5)P2, 188.8.131.52, Erk (MAPK1/3), MNK1, HIF1A, MEK2(MAP2K2), PTEN, Insulin receptor, mTOR, PI(3,4,5)P3, AKT(PKB)
Receptor-mediated HIF regulation
Insulin and Insulin-like growth factor 1 ( IGF-1 ) induce Hypoxia-inducible factor 1 alpha subunit ( HIF1A) ,  and HIF-induced Vascular endothelial growth factor ( VEGF ) expression , ,  and Insulin-like growth factor binding protein 3 ( IBP3 ) .
IGF-1 induces HIF1A protein synthesis via Mitogen-activated protein kinase 1 and 3 ( Erk (MAPK1/3) ) and Phosphoinositide-3-kinase ( PI3K )-dependent pathway that can involve Eukaryotic translation initiation factor 4E ( eIF4E ), Ribosomal protein S6 kinase 70kDa polypeptide (for example p70 S6 kinase2 )  and 3-phosphoinositide dependent protein kinase-1 ( PDK (PDPK1) )-dependent activation of FK506 binding protein 12-rapamycin associated protein 1 ( mTOR ) . IGF-1 binds IGF-1 receptor which possesses tyrosine kinase activity. IGF-1 receptor phosphorylates Insulin receptor substrate ( IRS ) and then IGF-1 receptor causes the sequential phosphorylation of PI3K, PDK, V-akt murine thymoma viral oncogene homolog 1 ( AKT(PKB) ), and mTOR. PI3K and PDK activation mediate IGF-1 -induced activation of p70 S6 kinase2 , . Recruitment to both IRS-1 and SHC transforming protein 1 ( Shc ) via the SH2 domain of the adaptor Growth factor receptor-bound protein 2 ( Grb2 ) leads to possible activation of V-Ha-ras Harvey rat sarcoma viral oncogene homolog ( H-Ras ) that in turn activates the protein serine kinase, possibly the V-raf-1 murine leukemia viral oncogene homolog 1 ( c-Raf-1 ), and ERK cascade . And then, via MAP kinase interacting serine/threonine kinase ( MNK ) and eIF4E, IGF-1 receptor induces HIF1A protein synthesis .
Insulin stimulates HIF1A through PI3K/ mTOR -dependent signaling pathway , . The binding of Insulin to the extracellular domain of the Insulin receptor results in the activation of the tyrosine kinase activity of the receptor. Insulin receptor via IRS activates the same PI3K -pathway as described above .