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IGF1R phosphorylates IRS1. 91 / 92
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"IGF1/IGF1R signal phosphorylates IRS1, activating PI3K and thereby also activating AKT."
32033461
sparser
"IGF1R phosphorylates IRS1 (Insulin receptor substrate-1) and recruits its downstream effectors ( xref )."
22343619
signor
"IGF-I binding to its receptor activates the kinase activity of the receptor, which then recruits the insulin response substrate-1, causing activation of phosphatidyl-inositol-3 kinase (PI3K) to phosphorylate Akt."
15829723
reach
"Hyperinsulinemia and elevated IGFR activates the phosphorylation of IRS-1, resulting in the activation of multiple cytokine pathways, including PI3K/AKT/mTOR and MAPK cascade, which modulate cell cycle and may potentially enhance tumor progression of HCC (35).3.2 Wnt/beta-catenin pathway."
37361533
reach
"IGF-1R activation leads to IRS-1 phosphorylation, which initiates recruitment of downstream effectors."
24844968
reach
"IGF-I rapidly stimulated beta-chain IGF-I receptor autophosphorylation, which peaked at a physiological and mitogenic concentration (1.4 nM) and also stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1)."
8756554
reach
"Otherwise, IGF-1R is activated through phosphorylation, and subsequently phosphorylates insulin receptor substrate 1 (IRS-1)."
29212962
reach
"Another study showed that concurrent blockade of IGF1R and its EGFR/Her-2 simultaneously inhibited the pancreatic tumor growth and the stimulation of IRS-1, Akt, and MAPK phosphorylation."
36556296
sparser
"Both IGF-I and IGF-II bind the tyrosine kinase receptor IGF1R, which in turn phosphorylates the insulin receptor substrates IRS-1 and IRS-2."
19261630
sparser
"Therefore, our studies define a unique signaling mechanism by which the IGF-I receptor phosphorylates IRS-1, allowing it to function as a molecular scaffold for assembly of a complex that is necessary to enable IGF-I to stimulate vimentin binding to RPTPβ ( xref )."
26773517
reach
"Rosiglitazone enhanced the phosphorylation of insulin receptor substrate 1 (IRS1, phosphorylated at Ser 636/639), which is considered to be the main activator of the Akt and mTOR pathway by IGF-1R."
28959186
rlimsp
"TNF-α also reduces phosphorylation of IRS-1 and IRS-2 by IGF1R, thus inhibiting signaling of IGF-1 in muscle cell development [46]."
22207907
sparser
"The activated IGF-1R recruits and phosphorylates the intracellular substrate IRS-1, and the phosphorylated IRS-1 is in turn recognized by SH2 domain–containing proteins, such as the p85 regulatory subunit of PI3K, and triggers activation of downstream signaling pathways."
33991522
reach
"Upon binding the IGF ligand, IGF1R is activated through autophosphorylation and subsequently phosphorylates insulin receptor substrate 1 (IRS1)."
27011182
trips
"In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished."
14559999
sparser
"Activation of PI3K thus requires both PKA-mediated relief of IRS1 inhibition and IGF-1R-dependent tyrosine phosphorylation of IRS1."
26702053
reach
"The phosphorylation of the IGF-I receptor beta subunit is coincidental with the tyrosine phosphorylation of its adapter IRS-1, suggesting that the IGF-I receptor phosphorylates IRS-1 in response to An[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10967198
sparser
"Upon engagement with IGFs, IGF1R phosphorylates IRS1, which then activates the PI3K/AKT/mTOR pathway to promote cartilage matrix synthesis [ xref , xref ]."
33639898
sparser
"Since activated IGF-1R phosphorylates IRS-1, we first examined whether TRAF4 affects IGF-1-induced IGF-1R activation in control or TRAF4-overexpressing MCF-7 cells."
33991522
sparser
"IGF-1R phosphorylates the insulin receptor substrate-1 (IRS-1) at the tyrosine site, leading to aberrant activation of downstream signaling pathways, such as the PI3K/Akt pathway [ 19–21 ]."
31461670
sparser
"Indeed, the effect of IGF1 is time-limited by the phosphorylation of IRS1 by IGF1R and its subsequent ubiquitination and proteasome-mediated degradation."
33466753
sparser
"Following IRS1 activation, IGF1R phosphorylates IRS1 leading to its ubiquitination by FBXO40 and its degradation by the 26S proteasome, in cultured myotube and in mice [ xref , xref ]."
33466753
rlimsp
"Notably, IL-1beta suppresses the ability of the IGF-I receptor tyrosine kinase to phosphorylate its major docking protein, insulin receptor substrate-1, in MCF-7 breast carcinoma cells."
15187102
reach
"It is widely known that the PI3K/Akt pathway is downstream of IRS-1, and IRS-1 could be phosphorylated by IGF-1R [ 22 ]."
31461670
rlimsp
"4F2 can inhibit IGF-IR autophosphorylation, IRS-1 phosphorylation and the activation of the major downstream signaling molecules AKT and mitogen-activated protein kinase."
22895605
reach
"Both IGF-I and IGF-II bind the tyrosine kinase receptor IGF1R, which in turn phosphorylates the insulin receptor substrates IRS-1 and IRS-2."
19261630
sparser
"Purified insulin receptor and IGF-I receptor phosphorylated recombinant baculovirus-produced IRS-1 on similar sites in vitro, and phosphorylated baculovirus-produced IRS-1 bound PtdIns 3'-kinase activity from lysates of quiescent cells."
8384986
reach
"1 Upon binding the IGF ligand, IGF-1R is activated through autophosporylation, and subsequently phosphorylates insulin receptor substrate 1 (IRS-1)."
25984556
reach
"The homologous insulin- like growth factor 1 receptor also phosphorylates IRS-1 in a similar manner [71."
8193539
sparser
"This would also suggest that, although IGF-1R-dependent IRS-1 phosphorylation is reduced in OA Obs, Syp phosphorylation and activity could compensate for this reduction."
17129375
rlimsp
"To test the function of the virally encoded receptors, we measured IGF-I stimulated autophosphorylation of the IGF-IR and phosphorylation of IRS-1."
12057025
rlimsp
"Binding of insulin/IGF-1 triggers a cascade of intracellular events beginning with receptor tyrosine phosphorylation; key residues include phosphorylation at tyrosine 1158/1162/1163 in IR or tyrosine 1131/1135/1136 in IGF-1R, which is indicative of enhanced activity [33,34]. The activated receptor phosphorylates substrates such as IRS1, which dock downstream effector molecules spanning a range of signaling pathways [35]."
26092184
sparser
"As for IGF1 induced phosphorylation of IRS1, the E3 ligase that modulates IRS1 levels after IGF1R phosphorylation of IRS1 is the Fbxo40–SCF complex (Shi et al ., xref ) ( xref )."
24237131
reach
"To analyze the mechanism by which stimulation of IGF-IR led to PKCzeta mediated vimentin phosphorylation, we determined if vimentin and PKCzeta were co-recruited to the scaffolding protein IRS-1, which is directly phosphorylated by IGF-IR."
26773517
sparser
"IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied."
9202243
rlimsp
"In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished."
14559999
sparser
"It is widely known that the PI3K/Akt pathway is downstream of IRS-1, and IRS-1 could be phosphorylated by IGF-1R [ 22 ]."
31461670
reach
"PIK3CA small interfering RNA (siRNA) silencing of p110α neither affected the increased phosphorylation of RTKs and IRS-1 nor total HER3 and IGF-1R levels (SI Appendix, Fig. S5), indicating that RTK activation by these driver mutations is p110α-independent.We established a CRISPR/Cas9-mediated W333R knock-in in the human colon cancer cell line HCT116, because PIK3R1 mutations frequently manifest in colon cancer patients."
34507989
reach
"Therefore, our studies define a unique signaling mechanism by which the IGF-I receptor phosphorylates IRS-1, allowing it to function as a molecular scaffold for assembly of a complex that is necessary to enable IGF-I to stimulate vimentin binding to RPTPbeta (XREF_FIG)."
26773517
reach
"We conclude that the human IL-4R has distinct domains that have predominant roles in growth stimulation and in gene induction; possession of the I4R motif alone, although allowing 4PS/IRS -1 phosphory[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
8624803
sparser
"One pathway involves IRS-1, which becomes tyrosine phosphorylated by IGF-IR and binds the Grb2/Sos complex through the SH2 domain of Grb2."
12837295
rlimsp
"Studies proved that intracellular domain of the IR is more effective in phosphorylating IRS-1 thus inducting the expression of genes involved in metabolic pathways; whereas, intracellular domain of IGF1R phosphorylate more potently Shc and Gab-1, which leads to the activation of genes involved in proliferation (Cai et al. 2017)."
30929166
reach
"Similarly, IGF-1R activation results in phosphorylation of the receptor substrate IRS-1 and activation of AKT at the cilium (Zhu et al., 2009)."
40257378
reach
"TNF-alpha also reduces phosphorylation of IRS-1 and IRS-2 by IGF1R, thus inhibiting signaling of IGF-1 in muscle cell development [XREF_BIBR]."
22207907
signor
"Binding of IGF1 to its receptor leads to activation of its intrinsic tyrosine kinase and autophosphorylation, thus generating docking sites for insulin receptor substrate (IRS), which is also phosphorylated by the IGF1 receptor."
21798082
reach
"In prostate cancer cells, co-inhibition of epidermal growth factor receptor and IGF-1R reduced phosphorylation of IRS-1 and its interaction with RAD51, suppressing HR and increasing radio-sensitivity [XREF_BIBR]."
26510816
reach
"IGF1R phosphorylates IRS1 (Insulin receptor substrate-1) and recruits its downstream effectors."
22343619
reach
"Indeed, IGF-IR internalization was required for Shc activation but not for IRS-1 phosphorylation, which was mediated by both cell surface and endosomal IGF-IR."
25566192
reach
"IGF-1 signaling begins when IGF-1 binds with its cell surface receptor, IGF-1R, forming a homodimer signaling complex, phosphorylating IGF-1R, which then phosphorylates intracellular insulin receptor substrate 1 (IRS-1) for its downstream targets."
25714651
reach
"The signaling cascade begins by the binding of ligand IGF (token number of 5) with the receptor (IGF-1R) which leads to the phosphorylation of IRS-1."
29787591
reach
"Another study from the same group [XREF_BIBR] established that phosphorylation of AKT on Thr308 and Ser473 increases following treatment of ALL cells with AICAR and demonstrated that AKT phosphorylation on Thr 308 is mediated by AMPK induced IGF-1R activation and phosphorylation of IRS-1."
22249159
sparser
"Generally, IGF1R is activated via autophosphorylation and subsequently phosphorylates IRS1 after IGF ligand binds to it."
28994330
reach
"Generally, IGF1R is activated via autophosphorylation and subsequently phosphorylates IRS1 after IGF ligand binds to it."
28994330
reach
"It markedly inhibited IRS1 and Shc phosphorylation and downregulated mitRaf.In addition, IGF-1R inhibition led to a decrease of cell survival and induced apoptosis in a manner depending on the approach used for the receptor inhibition, with IGF-1R-siRNA being the most effective apoptosis inducer.These findings suggest that blocking of several IGF1R signaling pathways may be necessary to effectively induce apotosis in lung cancer cells."
17454144
sparser
"Activated IGF-IR recruits and phosphorylates insulin receptor substrate proteins, IRS-1 and IRS-2 which in turn serve as multisite docking proteins by binding to numerous SH2 domain-containing protein[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
16843439
reach
"In the absence of IGF-I stimulation, or if mutated IGF-IR fails to phosphorylate IRS-1, localization of Rad51 to the sites of damaged DNA is diminished."
14559999
rlimsp
"These results showed that the mutant forms of IGF1R were capable of phosphorylating IRS-1 (Figure 4)."
22778948
sparser
"IGF-IR ligand binding causes phosphorylation of insulin receptor substrate-1 and -2 (IRS1, IRS2), which promote growth by transmitting signals to MAPK/ERK, PI3K/AKT and JAK/STAT in cell type specific manners [ xref , xref ]."
24565562
rlimsp
"Once stimulated, the tyrosine kinase activity of IGF-1R leads to its autophosphorylation as well as the phosphorylation of a number of intracellular proteins, such as IRS-1, Shc and Gab1."
17129375
reach
"In particular they act as competitive inhibitors of IGF-IR, promote inhibitory phosphorylation and degradation of IRS1 and IRS2 leading to the elimination of IRS1/2 and finally to cell death 27."
28369940
sparser
"Upon binding the IGF ligand, IGF1R is activated through autophosphorylation and subsequently phosphorylates insulin receptor substrate 1 (IRS1)."
27011182
reach
"A previous study showed that the simultaneous blockade of IGF1R and EGFR/HER2 synergistically inhibited pancreatic tumor growth and eliminated the activation of IRS-1, Akt, and MAPK phosphorylation."
37123059
sparser
"In cells only stimulated by IGF-I ( Fig. 8 A), the IGF-IR induces the tyrosine phosphorylation of IRS-1 which recruits docking proteins such as PI 3-kinase and initiates specific IGF-I downstream sign[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
23481042
sparser
"The phosphorylation of the IGF-I receptor β subunit is coincidental with the tyrosine phosphorylation of its adapter IRS-1, suggesting that the IGF-I receptor phosphorylates IRS-1 in response to AngII[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10967198
sparser
"Wheat germ agglutinin-purified mutant receptors were as active in phosphorylating poly-(Glu,Tyr) 4:1 as wild-type IGF-I receptors, suggesting that, in intact cells, additional factors are necessary in order for the IGF-I receptor to phosphorylate IRS-1."
7852347
sparser
"Phosphorylation of IRS1 by IGF1R further stimulated ubiquitin conjugation, consistent with the observation that IRS1 must be phosphorylated by IGF1R first, and only then is targeted for degradation by[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22033112
reach
"Upon engagement with IGFs, IGF1R phosphorylates IRS1, which then activates the PI3K/AKT/mTOR pathway to promote cartilage matrix synthesis [XREF_BIBR, XREF_BIBR]."
33639898
reach
"Activated igf1r phosphorylates specific reaction components, including IRS-1, IRS-2, and SRC homology collagen, and it regulates downstream responses through the phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways [1,37]."
35743889
sparser
"After the ligand binds to the receptor, IGF-1R will be activated via autophosphorylation and will phosphorylate the insulin receptor substrate 1 (IRS-1)."
32986356
sparser
"IGF-1R phosphorylates insulin receptor substrate 1 (IRS-1), which also contains pYXXM motifs that bind the SH2 domains of p85 [ xref ]."
18641990
rlimsp
"Consecutively, the activated IGF-IR directly phosphorylates other substrates such as IRS-1, IRS-2, and IRS-4 [57]."
26258011
reach
"Phosphorylation of IRS1 by IGF1R further stimulated ubiquitin conjugation, consistent with the observation that IRS1 must be phosphorylated by IGF1R first, and only then is targeted for degradation by[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
22033112
reach
"Compared to the immunoprecipitated IGF-IR from siCtrl cells, the immunoprecipitated IGF-IR from siGRP78 cells exhibited lower levels of tyrosine phosphorylation and induced lower levels of IRS1 phosph[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28389416
reach
"As for IGF1 induced phosphorylation of IRS1, the E3 ligase that modulates IRS1 levels after IGF1R phosphorylation of IRS1 is the Fbxo40 and SCF complex (XREF_FIG)."
24237131
sparser
"Activated PP1 is sufficient to dephosphorylate at least four IRS1 Ser residues, Ser 318 , Ser 346 , Ser 612 , and Ser 789 , and promotes IRS1 YXXM phosphorylation by the IGF1R to activate the PI3K/AKT cascade."
27856640
rlimsp
"The activated IGF-1R phosphorylates a major substrate, IRS1, on multiple sites, forming a signaling platform that stimulates mitogenic and survival pathways, including MAPK and PI3K [5]."
12559042
sparser
"TNF-α also reduces phosphorylation of IRS-1 and IRS-2 by IGF1R, thus inhibiting signaling of IGF-1 in muscle cell development [ xref ]."
22207907
sparser
"Downregulation of β 1 blocks IGF-stimulated cell proliferation and transformation of prostate cancer cells ( xref ), but the effect of β 1 downregulation on activation of IGF-IR and tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) has never been described."
20333644
rlimsp
"As for IGF1 induced phosphorylation of IRS1, the E3 ligase that modulates IRS1 levels after IGF1R phosphorylation of IRS1 is the Fbxo40–SCF complex (Shi et al., 2011) (Figure 1)."
24237131
rlimsp
"Interestingly, autophosphorylation of the IGF-IR and phosphorylation of the downstream substrate, insulin receptor substrate-1 (IRS-1), was not inhibited in doxycycline/IGF-I treated cells, suggesting the possibility that activation of downstream substrates other than the IRS-1 may be critical for optimal cell proliferation."
14709803
sparser
"InsR or IGF1R binds to IRS-1 via the phosphotyrosine-binding domain and phosphorylates multiple sites on tyrosine in IRS-1, leading to the association with several signaling molecules such as PI3K, GRB2 and SHP2 [ xref , xref ]."
30404198
reach
"While stimulation of IGF-1R by IGFs triggers autophosphorylation and subsequent phosphorylation of either insulin receptor substrate-1 (IRS-1) or insulin receptor substrate-2 (IRS-2), it is clear that these adapter proteins are activated by both IR 15 and IGF-1R."
29152592
rlimsp
"Moreover, the decrease in IGF-IR/pIGF-IR expression levels was associated with decreased phosphorylation of important IGF-IR targets including IRS-1, AKT, and NPM-ALK."
25884514
sparser
"Upon ligation, IGF1R recruits and phosphorylates IRS1."
30594912
reach
"Insulin receptor substrate 1 (IRS-1), which is known to be phosphorylated by autoactivated IGF-1R upon ligand binding, was shown to be involved in IGF-1R-mediated 4-OH-TAM resistance."
21595894
reach
"IGF-1R phosphorylates insulin receptor substrate 1 (IRS-1), which also contains pYXXM motifs that bind the SH2 domains of p85 [XREF_BIBR]."
18641990
rlimsp
"Another study from the same group [57] established that phosphorylation of AKT on Thr308 and Ser473 increases following treatment of ALL cells with AICAR and demonstrated that AKT phosphorylation on Thr 308 is mediated by AMPK-induced IGF-1R activation and phosphorylation of IRS-1."
22249159
reach
"61 Insulin receptor substrate-1 (IRS-1) levels, which is phosphorylated by IGF-IR activation, was found to predict worse disease-free survival in small (< 2 cm) OR negative tumours."
14687598
rlimsp
"IR and IGF1R are known to phosphorylate multiple IR substrates, including IRS-1, IRS-2, Shc, Gab-1 and Grb10 (ref."
28345670
rlimsp
"IGF-1R is a tyrosine kinase receptor that is activated by IGFs, the activated IGF-1R not only phosphorylates IRS-1 and SHC to activate the MAPK cascade, which stimulates cell growth and proliferation[11], but also protects from apoptosis as a result of activation of PI3K-Akt through phosphorylation and subsequent inactivation of BAD[12]."
24810113
sparser
"IGF-1R is a tyrosine kinase receptor that is activated by IGFs, the activated IGF-1R not only phosphorylates IRS-1 and SHC to activate the MAPK cascade, which stimulates cell growth and proliferation[ xref ], but also protects from apoptosis as a result of activation of PI3K-Akt through phosphorylation and subsequent inactivation of BAD[ xref ]."
24810113