IndraLab

"EGFR has three major autophosphorylation sites (Y1068, Y1148, and Y1173) in the C terminus.17 We designed 5- to 6-mer synthetic peptides that were derived from the amino acid sequences of these sites (EY1068INQ, PDY1148QQD, and AEY1173LR, respectively)."

"Moreover, previous study proved that PRMT5‐mediated EGFR Arg1175 methylation positively modulates EGF‐induced EGFR trans‐autophosphorylation at Tyr 1173, but have no effect on EGFR trans‐autophosphorylation at Tyr 1086, 845, 992, 1045 and 1148. xref Herein, we for the first time find that PRMT5 promotes the autophosphorylation of EGFR at Y1068 and Y1172 to activate Akt‐β‐catenin axis in pancreatic cancer cells."

"Moreover, previous study proved that PRMT5‐mediated EGFR Arg1175 methylation positively modulates EGF‐induced EGFR trans‐autophosphorylation at Tyr 1173, but have no effect on EGFR trans‐autophosphorylation at Tyr 1086, 845, 992, 1045 and 1148.17 Herein, we for the first time find that PRMT5 promotes the autophosphorylation of EGFR at Y1068 and Y1172 to activate Akt‐β‐catenin axis in pancreatic cancer cells."

"A previous study has been shown that PRMT5 regulates the autophosphorylation of EGFR at Tyr1068 and Tyr1172 to promotes EMT in pancreatic cancer cells [ xref ]."

"We have shown previously that tyrosine 1148 of the activated epidermal growth factor (EGF) receptor is a major binding site for Shc while tyrosine 1173 is a secondary binding site in intact cells. In the present study, we investigated the interaction between the PTB and SH2 domains of Shc and the activated human EGF receptor. Mutant 52-kDa Shc with an arginine-to-lysine substitution at residue 175 in the PTB domain (Shc R175K) or 397 in the SH2 domain (Shc R397K) was coexpressed in Chinese hamster ovary cells overexpressing the wild-type or mutant EGF receptors that retained only one of the autophosphorylation sites at tyrosine 1148 (QM1148) or 1173 (QM1173)."

"In this multimolecular complex, EGFR is phosphorylated in an EGF-independent manner on Y845, Y1068, Y1086, and Y1173, but not on Y1148, a major autophosphorylation site. The involvement of Src in these phosphorylations is not known; however, Src seems to be required for the recruitment of EGFR to the cell surface in response to integrin activation [153]. On the other hand, Wang et al. [154] have shown that, in squamous carcinoma cells, SCC12, the depletion of ganglioside GM3, which has been reported to be inhibitory to the integrin-dependent activation of EGFR, induces the phosphorylation of EGFR on Y845, Y1068, and Y1148, but not on Y1086 and Y1173."

"We have utilized site-directed mutants to study the role of autophosphorylation of the epidermal growth factor (EGF) receptor in the regulation of receptor kinase activity and ligand-induced endocytosis. A single mutation of the major autophosphorylation site, Y1173, and a double mutation of two autophosphorylation sites, Y1173 and Y1148, did not inhibit kinase activity in vivo, using PLC gamma 1 as a specific substrate for the EGF receptor kinase."

"MCL-1 antagonism also decreased the auto-phosphorylation site Y1148 in EGFR (–67%), proposed to be involved in the regulation of invasion by Src [34]."

"Phosphorylation of rasGAP by EGF receptor mutants, in which one to four autophosphorylation sites (Tyr-1173, -1148, -1086, and -1068) were mutated to phenylalanine, was reduced by 50-60% compared to the wild-type receptor. Elimination of these four autophosphorylation sites by truncation of 123 carboxyl-terminal residues of the EGF receptor paralleled results obtained with point mutants."

"MCL-1 antagonism also decreased the auto-phosphorylation site Y1148 in EGFR indicating suppression of invasion activity, perhaps due to loss of cSRC activation."

"Binding of EGF to the EGFR leads to the transphosphorylation of various tyrosine residues on the intracellular C-terminal tail. The tyrosine residues phosphorylated by EGF addition to cells include Y703, Y920, Y992, Y1045, Y1068, Y1086, Y1148, and Y1173. In addition to these autophosphorylated sites, there are also residues that are phosphorylated by other kinases, which interestingly appear downstream in the EGFR-activation cascade."

"The probe is shown to be a biased or partial allosteric agonist of the EGF receptor, inducing phosphorylation of Thr669 and Tyr992, but not the Tyr845, Tyr998, Tyr1045, Tyr1068, or Tyr1148 residues of the receptor, in the absence of the orthosteric EGF ligand. Additionally, the probe was found to suppress the EGF-stimulated autophosphorylation of these latter residues, indicating that it is also a noncompetitive antagonist."

"In intact cells we also show that Vav2 associates with the activated EGF receptor in an Src homology 2 domain-dependent manner, with Vav2 Src homology 2 domain binding preferentially to autophosphorylation sites Tyr-992 and Tyr-1148 of the EGF receptor."

"This was an interesting finding, as Tyr1173 rather than Tyr1148 is classically considered to be the dominant autophosphorylation site on EGFR (Voldborg et al., 1997 ▸)."

"We also detected autophosphorylated EGFR C-terminus (Y1197, Y1172), a critical region of EGFR that induces downstream ERK signaling through recruitment of SHC and GRB2."

"EGF clearly induced autophosphorylation of EGFR at Tyr1148 in four out of the five TC cell lines compared to the control (Figure 5), except for TT2609-C02, which harbors a NRAS mutation."