SHP2 is a downstream target of ZAP70 to regulate JAK1/STAT3 and ERK signaling pathways in mouse embryonic stem cells.
Previous research indicated that ZAP70, a Syk family tyrosine kinase, is expressed in mouse embryonic stem cells (mESCs) and regulates the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) signaling through consolidating SHP1 enzymatic activity. In this study, we report that SHP2 is another downstream target of ZAP70 in mESCs. We found that SHP2 phosphorylation and enzymatic activity are affected by Zap70 expression. In addition, we present evidence that ERK pathways activated by ZAP70 and SHP2 reduce the protein level of leukemia inhibitory factor (LIF) receptor. Based on these results, we propose that SHP2 is an essential mediator of the ZAP70 signal to regulate JAK1/STAT3 and ERK pathways in undifferentiated mESCs.
Cha
Young
Y
Department of Biomedical Science, College of Life Science, CHA Stem Cell Institute, CHA University, Pochon-si Gyeonggi-do, Republic of Korea.
Park
Kyung-Soon
KS
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D053613:Janus Kinase 1 / Q000378:metabolism*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507841:Lifr protein, mouse; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C516725:Ptpn11 protein, mouse