Open AccessZap70 Functions to Maintain Stemness of Mouse Embryonic Stem Cells by Negatively Regulating Jak1/Stat3/c‐Myc Signaling
Author(s) -
Cha Young,
Moon Bohyun,
Lee Miok,
Ahn Heejin,
Lee Hyejin,
Lee Kyungah,
Fornace Albert J.,
Kim Kwangsoo,
Cha Hyukjin,
Park Kyungsoon
Publication year - 2010
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.470
Subject(s) - biology , zap70 , microbiology and biotechnology , embryonic stem cell , protein tyrosine phosphatase , stat3 , stem cell , cellular differentiation , signal transduction , syk , regulator , tyrosine kinase , immunology , il 2 receptor , t cell , biochemistry , immune system , gene
Abstract Zeta‐chain‐associated protein kinase‐70 (Zap70), a Syk family tyrosine kinase, has been reported to be present exclusively in normal T‐cells, natural killer cells, and B cells, serving as a pivotal regulator of antigen‐mediated receptor signaling and development. In this study, we report that Zap70 is expressed in undifferentiated mouse embryonic stem cells (mESCs) and may critically regulate self‐renewal and pluripotency in mESCs. We found that Zap70 knocked‐down mESCs (Zap70KD) show sustained self‐renewal and defective differentiation. In addition, we present evidence that the sustained self‐renewal in Zap70KD is associated with enhanced Jak/Stat3 signaling and c‐Myc induction. These altered signaling appears to result from upregulated leukemia inhibitory factor receptor and downregulated src homology region 2 domain containing phosphatase 1 (SHP‐1) phosphatase activity. On the basis of these results, we propose that in undifferentiated mESCs, Zap70 plays important roles in modulating the balance between self‐renewal capacity and pluripotent differentiation ability as a key regulator of the Jak/Stat3/c‐Myc signaling pathway. S tem C ells 2010; 28:1476–1486.