Identification of a membrane-associated inhibitor(s) of epidermal growth factor-induced signal transducer and activator of transcription activation.
Many growth factors, including epidermal growth factor (EGF), can activate the signal transducer and activator of transcription (STAT) signaling pathway. Here, we demonstrate that STAT activation by EGF treatment is conditional. EGF activates STAT1 and STAT3 in A431 but not in HeLa and PC12 cells. Using a reconstituted in vitro STAT activation system, we have identified and partially purified a potential inhibitor (s) that is membrane-associated and can block STAT activation induced by EGF in vitro. However, this inhibitor has no effect on STAT complexes after they are formed. We have further shown that this inhibitor(s) also exists in many other cancer cell lines, suggesting that blocking the STAT activation during growth factor signal transduction may play a significant role in the development of many kinds of cancers.
Iwamoto
Y
Y
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Chin
Y E
YE
Peng
X
X
Fu
X Y
XY
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; D015534:Trans-Activators; D004815:Epidermal Growth Factor; D066246:ErbB Receptors