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SRC phosphorylates EGFR on tyrosine. 49 / 49
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"This paper reports that CDCP1 forms a ternary complex with Src and the EGFR, and that this complex mediates Src activation and Src dependent tyrosine phosphorylation of CDCP1 and EGFR (i.e., EGFR transactivation)."
27495374
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"The protein tyrosine kinase c-Src can directly phosphorylate Tyr residues in the kinase domain HER2 [ xref , xref ] and the cytoplasmic tail of EGFR [ xref ], allowing the formation of stable homo- or heterocomplexes with other receptors or the binding of scaffold proteins and the activation of signal transduction."
26114632
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"Activated Src leads to phosphorylation of epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases (RTK) that, in turn, activate diverse downstream intermediates of the signaling cascade, including phospholipase C (PLC-γ), G-protein Ras and mitogen-activated protein kinases (MAPK) [12] (Figure 7)."
28420099
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"For example, activation of the G i -coupled lysophosphatidic acid receptor has been reported to elicit the transactivation and tyrosine phosphorylation of the epidermal growth factor receptor by a PTX[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
10930532
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"Src phosphorylates tyr845 on the epidermal growth factor receptor to activate the receptor tyrosine kinase which in turn phosphorylates and activates phospholipase Cgamma."
25748412
rlimsp
"This synergy is dependent upon c-Src-mediated phosphorylation of a unique tyrosine on the EGFR, namely, tyrosine 845 (Y845)."
15282306
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"The EGFR can be transactivated either by enhanced “inside-out signaling” that would increase cell surface shedding of EGFR ligands such as pro HB-EGF by stimulating metalloproteinases of the ADAM (a disintegrin and metalloproteinase) family ( xref ; xref ; xref ) or by intracellular activation of non-receptor tyrosine kinase c-Src ( xref ), which phosphorylates the EGFR on tyrosine residue 845 and 1101 and results in receptor activation ( xref )."
19151764
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"This sustained EGFR transactivation is mainly due to Src kinase mediated persistent EGFR tyrosine phosphorylation at Y845 rather than Y1173."
28943431
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"As a consequence, Src phosphorylates EGFR at two tyrosine residues to promote EGF receptor activity ( Biscardi et al., 1999 )."
16860569
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"For example, Src phosphorylates EGFR on tyrosine residues that are distinct from EGFR autophosphorylation sites, and these transactivation sites couple to downstream PI3K activation more effectively than the EGFR autophosphorylation sites [XREF_BIBR]."
27495374
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"Surprisingly, c-Src inactivation through caspase-8 knockdown or dasatinib was able to block the survival-signaling-related tyrosine phosphorylation of EGFR, which, in turn, increased the antitumor activity of TKIs in EGFR-mutant lung adenocarcinoma."
34367939
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"C-Src can phosphorylate EGFR tyrosine residues which directly modulate EGFR activity (Biscardi et al., 1999)."
24501773
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"These observations suggest that CRF promotes the formation of a multiprotein complex that would allow rapid EGFR phosphorylation at Tyr by Src, present in this complex.It has been shown that, in parallel to Src activation by many GPCRs, the proline-rich tyrosine kinase 2, PYK2, is also phosphorylated and activated, and in association with Src is required for the subsequent transactivation of EGFR (44, 48)."
31920979
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"For beta1 integrin coupled EGFR activation, adhesion dependent Src activation seems to be crucial [17], and active Src, unlike soluble EGF, phosphorylates EGFR at tyrosine (Y) 845 and not at one of th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26079101
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"While c-Src induces phosphorylation of the EGFR at critical activating tyrosine residues ( Biscardi et al. 1999; Tice et al. 1999 ), the suppressing effect of Fyn on EGFR activation is not due to incr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11106751
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"Biscardi and colleagues found that Src was able to phosphorylate EGFR at two unique tyrosine residues, distinct from the autophosphorylation sites, to activate EGFR, in association with the activation[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12888263
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"Conversely, Src can phosphorylate the EGFR kinase at a specific tyrosine residue (Y845), resulting in downstream activation of Ras/MAPK ( xref )."
33294779
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"Although the functional connection between Src and the EGFR is still unclear, EGFR tyrosine phosphorylation by Src was shown to be crucial for EGF induced and LPA induced mitogenic responses [XREF_BIBR]."
11250708
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"Basal breast cancer cells are characterized by elevated tyrosine phosphorylation of Met, Lyn, EphA2, epidermal growth factor receptor (EGFR), and FAK, and Src family kinase (SFK) substrates such as p130Cas."
20861192
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"Biscardi and colleagues found that Src was able to phosphorylate EGFR at two unique tyrosine residues, distinct from the autophosphorylation sites, to activate EGFR, in association with the activation[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12888263
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"Two well-known mechanisms of EGFR transactivation are : (1) extracellular cleavage of membrane bound EGFR ligands by activated MMPs or ADAMs that can then engage the receptor, and (2) intracellular phosphorylation of EGFR tyrosine residues by Src kinases [XREF_BIBR, XREF_BIBR]."
28671992
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"A common kinase activated by membrane-associated ER and plays a critical role in EGFR activation is Src, and it has been well-established that Src can phosphorylate EGFR on tyrosine residue Y845 ( xref ; xref )."
31468104
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"Within this complex beta1 integrin became activated thereby inducing a c-Src-dependent EGFR phosphorylation at Y 1086 and Y 1173 EGF-independent residues."
27713116
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"While c-Src induces phosphorylation of the EGFR at critical activating tyrosine residues (Biscardi et al. 1999; Tice et al. 1999), the suppressing effect of Fyn on EGFR activation is not due to increa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
11106751
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"PLCgamma-1 and c-Src bind directly or indirectly to phosphorylated tyrosine residues on EGFR."
18594017
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"Two well-known mechanisms of EGFR transactivation are: (1) extracellular cleavage of membrane-bound EGFR ligands by activated MMPs or ADAMs that can then engage the receptor, and (2) intracellular phosphorylation of EGFR tyrosine residues by Src kinases [ xref , xref ]."
28671992
rlimsp
"We show that Src kinases are critical for activation of Pyk2 in response to GPCR-stimulation and that Pyk2 and Src are essential for GPCR-induced tyrosine phosphorylation of EGFR."
11274221
rlimsp
"Later, Wasilenko et al. [39] made the first demonstration that Src is capable of phosphorylating EGFR on unknown tyrosine residue(s)."
23702846
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"If Src only selectively phosphorylates some tyrosine residues of EGFR, what downstream signaling pathways will be active by this partially activated EGFR?"
26771606
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"Activated Src, in turn, phosphorylates EGFR on selected tyrosine residues, leading to enhanced cell migration, cell proliferation and tumor growth."
19074873
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"Src activation, however, can lead to phosphorylation of additional tyrosine residues of the EGFR (i.e., at positions 703, 845, 1101, 1148, and 1173)."
19074873
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"Activated Src, in turn, can induce the phosphorylation of EGFR on selected tyrosine residues (i.e., 845 and 1173), leading to enhanced cell proliferation (XREF_FIG) and migration (XREF_SUPPLEMENTARY)."
19074873
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"C-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes."
11749381
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"If Src only selectively phosphorylates some tyrosine residues of EGFR, what downstream signaling pathways will be active by this partially activated EGFR?"
26771606
rlimsp
"For example, Src phosphorylates EGFR on tyrosine residues that are distinct from EGFR autophosphorylation sites, and these transactivation sites couple to downstream PI3K activation more effectively than the EGFR autophosphorylation sites [56]."
27495374
rlimsp
"In addition to the extracellular domain, EGFR contains a single transmembrane domain at almost the center of the protein (green) and a carboxyl-terminal sequence that contains the catalytic/kinase domain (red) and a non-catalytic tail sequence (yellow), between the two where the Src phosphorylation site Y845 and several tyrosine residues to be autophosphorylated are located."
23702846
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"SRC has been show to induce EGFR tyrosine phosphorylation [45], and inhibition of SRC by saracatinib would therefore also inhibit EGFR phosphorylation leading to an inhibition of EphA2 expression."
19948216
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"It is now known that c-Src is capable of phosphorylating EGFR on four major tyrosine residues: 845, 891, 920, and 1101 [ xref ]."
27086143
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"In this context, previous research has established that Src can activate EGFR signaling by phosphorylating Tyr of the EGFR protein (45, 46)."
31920979
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"In COS-7 cells, Src was reported to induce EGFR tyrosine phosphorylation after stimulation of the G i -coupled LPA and alpha 2A -adrenergic receptors or overexpression of Gbetagamma subunits, independently of the intrinsic kinase activity of EGFR [XREF_BIBR]."
11250708
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"Two central mechanisms have been proposed, namely, phosphorylation of the EGFR by the nonreceptor tyrosine kinase Src [7,17-20], and matrix metalloproteinase (MMP)-mediated release of EGFR ligands [20[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
14568001
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"Conversely, Src can phosphorylate the EGFR kinase at a specific tyrosine residue (Y845), resulting in downstream activation of Ras and MAPK."
33294779
rlimsp
"These studies suggest that EGFR and Src communicate with each other by Src-dependent phosphorylation of novel tyrosine residues (for review, see [4,43–46])."
23702846
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"Alternatively, the Src non-receptor kinase can phosphorylate EGFR at tyrosine residues 845 and 1101 ( xref , xref )."
18698032
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"Activated Src, in turn, can induce the phosphorylation of EGFR on selected tyrosine residues (i.e., 845 and 1173), leading to enhanced cell proliferation ( xref ) and migration ( xref )."
19074873
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"As a consequence, Src phosphorylates EGFR at two tyrosine residues to promote EGF receptor activity (Biscardi et al., 1999)."
16860569
rlimsp
"A mutant P2Y(2) receptor lacking the PXXP motifs was found to stimulate calcium mobilization and serine/threonine phosphorylation of the Erk1/2 mitogen-activated protein kinases, like the wild-type receptor, but was defective in its ability to stimulate tyrosine phosphorylation of Src and Src-dependent tyrosine phosphorylation of the proline-rich tyrosine kinase 2, epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor."
14670955
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"This sustained EGFR transactivation is mainly due to Src mediated persistent EGFR tyrosine phosphorylation at Y845 rather than Y1173."
28943431
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"Collectively, these results indicate that upon As 2 O 3 treatment, Src activity contributes to EGFR tyrosine phosphorylation and its interaction with downstream adaptor molecules (ShcA and Grb2) with contrasting characteristics to that of EGF mediated EGFR/Shc/Grb2 interactions."
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