EGF receptor deletions define a region specifically mediating STAT transcription factor activation.
Binding of EGF to its cognate receptor results in receptor-dimerisation, auto-phosphorylation and activation of intracellular signal transduction pathways. Autophosphorylated tyrosine residues in the receptor complex bind to SH2-domain containing signalling molecules and these are then often themselves phosphorylated by the receptor kinase. A critical role for these SH2-binding sites, however, is unclear. We have investigated the stimulation of (SH2-domain containing) STAT transcription factor activity, in comparison with MAP kinase activity, in cell lines expressing EGF receptor deletion mutations. Data indicate that two autophosphorylated tyrosine residues Y1068 and Y1086 are critical for STAT activation in contrast to MAP kinase activation. Significantly, these tyrosine residues conform to a consensus YXXQ binding site and suggest direct binding of STAT-proteins to the EGF receptor.
Coffer
P J
PJ
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Kruijer
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D050794:STAT1 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1