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EGFR — FAS
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
FADD
→
Complex of EGFR-FAS
(increases, EGFR/FAS Activity, FADD Translocation)
Reinehr et al., J Biol Chem 2005*
Evidence: Activated Yes rapidly associated with the epidermal growth factor receptor (EGFR), which became phosphorylated at Tyr845 and Tyr1173 but not at Tyr1045. Activated EGFR then triggered an AG1478-sensitive CD95-tyrosine phosphorylation, which was a signal for membrane targeting of the EGFR/CD95 complex, subsequent recruitment of Fas-associated death domain and caspase 8, and apoptosis induction. All of these events were significantly blunted by inhibitors of sphingomyelinase, PKCzeta, NADPH oxidase...
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Reinehr et al., FASEB J 2003
:
Inhibition of
EGFR tyrosine kinase activity
prevented CD95 tyrosine phosphorylation and DISC formation but not hyperosmolarity induced EGFR phosphorylation and EGFR association with CD95 ... Stimulation of
EGFR by EGF
induced EGFR phosphorylation but no association with
CD95 or CD95 phosphorylation
Reinehr et al., Gastroenterology 2003
:
Bile salt induced hepatocyte apoptosis involves
epidermal growth factor receptor dependent
CD95 tyrosine phosphorylation ... Induction of apoptosis by hydrophobic bile salts involves EGF-R activation and
EGF-R dependent
CD95 tyrosine phosphorylation, which triggers CD95 membrane targeting and Fas associated death domain/caspase-8 recruitment
Reinehr et al., J Biol Chem 2004
:
Epidermal growth factor receptor dependent
CD95-tyrosine phosphorylation was recently identified as an early step in apoptosis induction via the CD95 system ( Reinehr, R., Schliess, F., and Häussinger, D. ( 2003 ) FASEB J. 17, 731-733 )
Eberle et al., Hepatology 2005
:
Hyperosmolarity- and
CD95 ligand (CD95L) induced interactions between CD95 ( Fas/APO-1 ) and the
epidermal growth factor receptor (EGFR) involve EGFR catalyzed CD95 tyrosine phosphorylation ... Inhibition of
EGFR tyrosine kinase activity by AG1478 and cyclic adenosine monophosphate had no effect on hyperosmotic CD95-EGFR association in the cytosol but
prevented CD95 tyrosine phosphorylation, targeting of the protein complex to the plasma membrane, and formation of the death inducing signaling complex ( DISC ) ... The requirement of
EGFR mediated
CD95 tyrosine phosphorylation for hyperosmotic and CD95L induced CD95 membrane targeting and DISC formation was also shown in CD95 mutagenesis experiments ... CD95 mutants with tyrosine-phenylalanine exchanges at positions 232 and 291 failed to translocate to the plasma membrane and to recruit Fas associated death domain and caspase 8, although these mutants still associated with the
EGFR in the cytosol in
response to hyperosmolarity and
CD95L
Reinehr et al., J Biol Chem 2005
:
Activated
EGFR then
triggered an AG1478-sensitive
CD95-tyrosine phosphorylation, which was a signal for membrane targeting of the EGFR/CD95 complex, subsequent recruitment of Fas associated death domain and caspase 8, and apoptosis induction
Weng et al., Toxicol Appl Pharmacol 2007
(Breast Neoplasms...) :
Furthermore, treatment with kinase inhibitors of EGFR and ErbB-2 suggested that
EGFR/ErbB-2 activation was
involved in EGF induced
FAS expression ... The PI 3-kinase inhibitors and tyrosine kinase inhibitors of
EGFR and ErbB-2 also
reduced constitutive
FAS expression
Eberle et al., Apoptosis 2007
:
FRET-studies in mouse embryonic fibroblasts, which in contrast to Huh7 express endogenous CD95, revealed that EGF, but not
CD95L induced
EGFR-homomerization , whereas CD95 ligand, but not EGF resulted in EGFR/CD95-heteromerization
Iwase et al., Oral Oncol 2008
(Carcinoma, Squamous Cell...) :
Although
EGFR inhibitors did not
affect the expression of
Fas , the Fas associated death domain protein, or procaspase-8 in OSCC cells, the inhibition downregulated cellular FLICE-inhibitory protein ( c-FLIP )
Reinehr et al., Gastroenterology 2008
(Disease Models, Animal...) :
In quiescent HSCs,
CD95L led to a rapid phosphorylation of the
epidermal growth factor receptor (EGFR) , extracellular signal regulated kinase ( Erk ), and c-Src, but not of c-Jun-N-terminal kinase and p47(phox), an activating subunit of reduced nicotinamide adenine dinucleotide phosphate oxidase ...
CD95L induced
EGFR and Erk phosphorylation were abolished after proteinase inhibition by GM6001 and in the presence of neutralizing epidermal growth factor antibodies, suggestive of a ligand dependent EGFR phosphorylation in response to CD95L
Mao et al., Development 2009
:
No significant genetic interactions were detected with the Notch, Wingless, Hedgehog or Dpp pathways, nor did Fas2 inhibit the FGF receptor or Torso, indicating specificity in the inhibitory
role of
Fas2 in
EGFR signalling
Sommerfeld et al., J Biol Chem 2009
:
When, however, a JNK signal was induced by coadministration of cycloheximide or hydrogen peroxide ( H2O2 ), activated EGFR associated with CD95 and triggered
EGFR mediated
CD95-tyrosine phosphorylation and subsequent formation of the death inducing signaling complex
Lokeshwar et al., Cancer Res 2010
(Neoplasm Invasiveness...) :
4-MU
induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, upregulation of Fas-L,
Fas , FADD and DR4, and downregulation of bcl-2, phosphorylated bad, bcl-XL, phosphorylated Akt, phosphorylated IKB, phosphorylated ErbB2, and phosphorylated
epidermal growth factor receptor
Reinehr et al., Arch Biochem Biophys 2012
:
Then the
role of
EGFR in activating
CD95 death receptor in liver parenchymal cells ( PC ) and hepatic stellate cells (HSC), which represent a liver stem/progenitor cell compartment, is described summarizing different ways of CD95- and EGFR dependent signaling in the liver