SHP2 is a downstream target of ZAP70 to regulate JAK1/STAT3 and ERK signaling pathways in mouse embryonic stem cells

Young Cha; Kyung-Soon Park

doi:10.1016/j.febslet.2010.09.016

SHP2 is a downstream target of ZAP70 to regulate JAK1/STAT3 and ERK signaling pathways in mouse embryonic stem cells

FEBS Lett. 2010 Oct 8;584(19):4241-6. doi: 10.1016/j.febslet.2010.09.016. Epub 2010 Sep 17.

Authors

Young Cha¹, Kyung-Soon Park

Affiliation

¹ Department of Biomedical Science, College of Life Science, CHA Stem Cell Institute, CHA University, Pochon-si Gyeonggi-do, Republic of Korea.

PMID: 20846526
DOI: 10.1016/j.febslet.2010.09.016

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cells, Cultured
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Knockdown Techniques
Janus Kinase 1 / metabolism*
Leukemia Inhibitory Factor Receptor alpha Subunit / metabolism
MAP Kinase Signaling System
Mice
Models, Biological
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
RNA, Small Interfering / genetics
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
STAT3 Transcription Factor / metabolism*
Signal Transduction
Transfection
ZAP-70 Protein-Tyrosine Kinase / antagonists & inhibitors
ZAP-70 Protein-Tyrosine Kinase / genetics
ZAP-70 Protein-Tyrosine Kinase / metabolism*

Substances

Leukemia Inhibitory Factor Receptor alpha Subunit
Lifr protein, mouse
RNA, Small Interfering
Recombinant Proteins
STAT3 Transcription Factor
Stat3 protein, mouse
Jak1 protein, mouse
Janus Kinase 1
ZAP-70 Protein-Tyrosine Kinase
Zap70 protein, mouse
Extracellular Signal-Regulated MAP Kinases
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Ptpn11 protein, mouse