The insulin receptor (IR), insulin-like growth factor receptor (IGFR), and insulin-receptor-related receptor (IRR) form a subgroup of receptor tyrosine kinases involved in regulating cellular growth and organismal metabolism. The activated IR regulates cellular uptake and metabolism of fuels, while the activated IGFR promotes cell growth, survival, and differentiation. Knockout mice studies have revealed the IGF-I receptor mediates IGF-I and IGF-II action on prenatal growth as well as IGF-I action on postnatal growth. The IR mediates prenatal growth in response to IGF-II and postnatal growth in response to insulin. All of these receptors share extensive structural homology and utilize the same downstream signalling cascades, one of which is illustrated here. Thus, how specificity is achieved in physiological outputs remains unclear, although it is thought to occur, in part, by differences in the locations and levels of receptor expression. Medline=11737239 Medline=11739335 Medline=11897402 Medline=12169433 Medline=12175645 Medline=12360255 4.0 s5 PROTEIN p2 s5 PROTEIN p1 s59 PROTEIN p14 s59 PROTEIN p33 s68 PROTEIN p26 s68 PROTEIN p25 s71 PROTEIN p25 s71 PROTEIN p26 SQUARE_CLOSEUP_NORTH OVAL inactive inactive active inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive active active inactive inactive inactive inactive active active inactive inactive inactive inactive inactive inactive inactive active inactive inactive active inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive active active inactive inactive inactive inactive inactive inactive inactive inactive Cytosol Nucleus Long Name: ATP Synonym: Synonym not specified Accession: S01736 inside SIMPLE_MOLECULE ATP Long Name: ADP Synonym: Synonym not specified Accession: S01739 inside SIMPLE_MOLECULE ADP Long Name: Insulin/Insulin like growth factor Synonym: IGF,IGF1,IGF2,Insulin like growth factor 1,Insulin like growth factor 2 Accession: P00896 inside PROTEIN p2 Long Name: Insulin receptor substrate family Synonym: IRS Accession: P00899 inside PROTEIN p4 Long Name: Insulin receptor substrate family Synonym: IRS Accession: P00899 inside PROTEIN p4 Long Name: Insulin receptor/Insulin like growth factor receptor/insulin related receptor Synonym: IGF-R,IGF-R1,IGF-R2,INSR,IRR,Insulin R,Insulin like growth factor receptor 1,Insulin like growth factor receptor 2 Accession: P00895 transmembrane PROTEIN p1 Long Name: Long name not specified Synonym: Synonym not specified Accession: U05321 Heterodimer Member Info: INSR IGF-R IRR#PROTEIN#Insulin receptor/Insulin like growth factor receptor/insulin related receptor#P00895#IGF-R|IGF-R1|IGF-R2|INSR|IRR|Insulin R|Insulin like growth factor receptor 1|Insulin like growth factor receptor 2#;Insulin IGF#PROTEIN#Insulin/Insulin like growth factor#P00896#IGF|IGF1|IGF2|Insulin like growth factor 1|Insulin like growth factor 2# transmembrane COMPLEX Complex_br_(Insulin_br_IGF/INSR_br_IGF_minus_R_br_IRR) Long Name: Phosphatidylinositol 3-kinase Synonym: PI3-K,PI3K,Phosphoinositide 3-OH-kinase,Phosphoinositide 3-kinase Accession: P00900 inside PROTEIN p14 Long Name: PiP2 Synonym: Synonym not specified Accession: S01738 inside SIMPLE_MOLECULE PiP2 Long Name: PiP3 Synonym: Synonym not specified Accession: S01737 inside SIMPLE_MOLECULE PiP3 Long Name: Phosphatase and tensin homolog Synonym: PTEN,Phosphatidylinositol phosphate phosphatase,PtdIns phosphate phosphatase Accession: P00905 inside PROTEIN p15 Long Name: SH2 domain-containing inositol 5-phosphatase 2 Synonym: INPP5D,Inositol polyphosphate-5-phosphatase,SHIP2 Accession: P00897 inside PROTEIN p16 Long Name: 3-phosphoinositide-dependent protein kinase Synonym: Synonym not specified Accession: P00903 inside PROTEIN p17 Long Name: Glycogen synthase kinase 3 Synonym: Synonym not specified Accession: P00902 inside PROTEIN p21 Long Name: Glycogen synthase kinase 3 Synonym: Synonym not specified Accession: P00902 inside PROTEIN p21 Long Name: Glycogen synthesis Synonym: Synonym not specified Accession: U02393 inside PHENOTYPE Glycogen synthesis Long Name: ATP Synonym: Synonym not specified Accession: S01736 inside SIMPLE_MOLECULE ATP Long Name: ADP Synonym: Synonym not specified Accession: S01739 inside SIMPLE_MOLECULE ADP Long Name: p53 Synonym: Synonym not specified Accession: P04497 Pathway Link: P00006|P00273|Apoptosis signaling pathway*P04397|P04640|p53 pathway by glucose deprivation*P04398|P04668|p53 pathway feedback loops 2*P04392|P04539|P53 pathway feedback loops 1*P00059|P01485|p53 pathway inside PROTEIN p23 Long Name: PTEN Synonym: Synonym not specified Accession: G04675 inside GENE gn1 Long Name: Mdm2 Synonym: Synonym not specified Accession: P04496 Pathway Link: P04398|P04663|p53 pathway feedback loops 2*P04392|P04536|P53 pathway feedback loops 1*P00059|P01483|p53 pathway inside PROTEIN p24 Long Name: Mdm2 Synonym: Synonym not specified Accession: P04496 Pathway Link: P04398|P04663|p53 pathway feedback loops 2*P04392|P04536|P53 pathway feedback loops 1*P00059|P01483|p53 pathway inside PROTEIN p24 Long Name: Mdm2 Synonym: Synonym not specified Accession: G04674 inside GENE gn2 Long Name: p53 Synonym: Synonym not specified Accession: P04497 Pathway Link: P00006|P00273|Apoptosis signaling pathway*P04397|P04640|p53 pathway by glucose deprivation*P04398|P04668|p53 pathway feedback loops 2*P04392|P04539|P53 pathway feedback loops 1*P00059|P01485|p53 pathway inside PROTEIN p23 Long Name: P110alpha Synonym: P110-alpha,PIK3CA Accession: P04498 inside PROTEIN p33 Long Name: p110alpha Synonym: P110-alpha,PIK3CA Accession: G04676 inside GENE gn3 Long Name: Long name not specified Synonym: Synonym not specified Accession: U05320 Heterodimer Member Info: PI3-K#PROTEIN#Phosphatidylinositol 3-kinase#P00900#PI3-K|PI3K|Phosphoinositide 3-OH-kinase|Phosphoinositide 3-kinase#;P110alpha#PROTEIN#P110alpha#P04498#P110-alpha|PIK3CA# inside COMPLEX Complex_br_(PI3_minus_K/P110_alpha_) Long Name: P53 pathway Synonym: Synonym not specified Accession: U05325 inside PHENOTYPE P53_space_pathway Long Name: Cell growth low ROS high HSP Synonym: Synonym not specified Accession: U05326 inside PHENOTYPE Cell growth_br_low_space_ROS_br_high HSP Long Name: Forkhead transcription factor Synonym: FOXO1A,Forkhead box O1A,Forkhead in rhabdomyosarcoma Accession: P00898 inside PROTEIN p20 Long Name: Forkhead transcription factor Synonym: FOXO1A,Forkhead box O1A,Forkhead in rhabdomyosarcoma Accession: P00898 inside PROTEIN p20 Long Name: Forkhead transcription factor Synonym: FOXO1A,Forkhead box O1A,Forkhead in rhabdomyosarcoma Accession: P00898 inside PROTEIN p20 Long Name: p27 Apoptosis Synonym: Synonym not specified Accession: U05327 inside PHENOTYPE p27_br_Apoptosis Long Name: Cell survival Synonym: Synonym not specified Accession: U02392 inside PHENOTYPE Cell survival_br_maintenance Long Name: Hamartin Synonym: Tuberous sclerosis-1 Accession: P04495 inside PROTEIN p26 Long Name: Long name not specified Synonym: Synonym not specified Accession: U05323 Heterodimer Member Info: Tsc2#PROTEIN#Tuberin#P04494##;Tsc1#PROTEIN#Hamartin#P04495#Tuberous sclerosis-1# inside COMPLEX Complex_br_(Tsc1/Tsc2) Long Name: Tuberin Synonym: Synonym not specified Accession: P04494 innerSurface PROTEIN p25 Long Name: Glucose depreivation response Synonym: Synonym not specified Accession: U05324 inside PHENOTYPE Glucose depreivation_br_response Long Name: Long name not specified Synonym: Synonym not specified Accession: U05322 Heterodimer Member Info: Tsc2#PROTEIN#Tuberin#P04494##;Tsc1#PROTEIN#Hamartin#P04495#Tuberous sclerosis-1# inside COMPLEX Complex_br_(Tsc2/Tsc1) Long Name: Protein kinase B Synonym: AKT,PKB Accession: P00894 Pathway Link: P04397|P04641|p53 pathway by glucose deprivation*P04398|P04665|p53 pathway feedback loops 2*P00059|P01486|p53 pathway inside PROTEIN p18 Long Name: Protein kinase B Synonym: AKT,PKB Accession: P00894 Pathway Link: P04397|P04641|p53 pathway by glucose deprivation*P04398|P04665|p53 pathway feedback loops 2*P00059|P01486|p53 pathway inside PROTEIN p18 inside RNA rn1 inside RNA rn2 inside RNA rn3 inside DEGRADED s77 HETERODIMER_ASSOCIATION 0.33333333333333304,1.7763568394002505E-15 0.666666666666667,0.0 0.3333333333333348,0.0 0.6666666666666679,-8.881784197001252E-16 0.33333333333333304,-5.551115123125783E-17 0.6666666666666661,-2.7755575615628914E-16 0.3333333333333339,0.3333333333333335 a2 a1 a5 STATE_TRANSITION 0.33333333333333215,4.884981308350689E-15 0.666666666666667,9.547918011776346E-15 a7 a9 a8 a10 a5 STATE_TRANSITION 0.3184079601990044,0.13432835820895495 0.6741293532338313,0.13432835820895495 a48 a49 a88 STATE_TRANSITION 0.33333333333333304,0.08955223880596996 0.6592039800995022,0.08208955223880565 a49 a48 a51 a50 STATE_TRANSITION 0.3333333333333335,8.881784197001252E-16 0.6666666666666669,1.3322676295501878E-15 a52 a56 a49 STATE_TRANSITION 0.3333333333333335,4.440892098500626E-16 0.6666666666666666,4.440892098500626E-16 a53 a59 a57 a60 a56 STATE_TRANSITION 0.33333333333333215,0.0 0.666666666666667,0.0 a65 a68 a62 a70 a57 STATE_TRANSITION 0.33333333333333215,0.0 0.6666666666666661,0.0 a66 a69 a61 a71 a57 TRANSPORT 0.3333333333333335,0.0 0.6666666666666665,0.0 a61 a76 STATE_TRANSITION 0.3333333333333339,-2.220446049250313E-16 0.6666666666666661,-5.551115123125783E-16 a80 a81 a57 STATE_TRANSITION 0.33333333333333326,0.0 0.6666666666666663,0.0 a84 a77 HETERODIMER_ASSOCIATION 0.507987010439015,0.02624015028162674 0.513598653608371,-0.015028876061862206 0.5174943161043193,2.776610767298848E-4 0.3333333333333339,0.3333333333333328 a46 a85 a88 a8 STATE_TRANSITION 0.3333333333333339,1.7763568394002505E-15 0.6666666666666679,-1.7763568394002505E-15 a104 a110 a57 DISSOCIATION 0.3333333333333339,1.3322676295501878E-15 0.6666666666666661,4.440892098500626E-16 0.33333333333333215,0.0 0.6666666666666643,-3.552713678800501E-15 0.33333333333333215,-1.7763568394002505E-15 0.6666666666666679,-8.881784197001252E-16 0.33333333333333215,0.3333333333333357 a110 a106 a107 TRANSLATION 0.3886966693248898,0.04771063797436703 0.7041359728012512,0.03109711225115319 a82 a80 TRANSLATION 0.29507275689644974,-0.026967807180173775 0.628406090229781,-0.02696780718017555 a86 a85 TRANSLATION 0.04815052936541209,-0.12060216103735577 0.4849117102274336,-0.07815145642500987 a78 a50 TRANSCRIPTION sa51 a86 a77 TRANSCRIPTION sa52 a78 a77 TRANSCRIPTION sa53 a82 a77 STATE_TRANSITION a77 sa57 a80 PHYSICAL_STIMULATION a77 a89 PHYSICAL_STIMULATION a81 a89 PHYSICAL_STIMULATION a65 a72 PHYSICAL_STIMULATION a66 a93 PHYSICAL_STIMULATION a61 a73 PHYSICAL_STIMULATION a76 a92 PHYSICAL_STIMULATION a104 a108