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Expression profiles of protein tyrosine kinase genes in human embryonic stem cells

M Son, Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea, Republic of
J Kim, Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejoen, Korea, Republic of
H Han, Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea, Republic of
S Woo, Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea, Republic of
Y Cho, Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea, Republic of
Y Kang, Regenerative Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea, Republic of
Y Han, Department of Biological Sciences and Center for Stem Cell Differentiation, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea, Republic of

Correspondence: Mi-Young Son, Email: myson{at}kribb.re.kr

Abstract

Complex signaling pathways operate in human embryonic stem cells (hESCs) and are coordinated to maintain self-renewal and stem-cell characteristics in them. Protein tyrosine kinases (PTKs) participate in diverse signaling pathways in various types of cells. Because of their functions as key molecules in various cellular processes, PTKs are anticipated to have important roles also in hESCs. In this study, we investigated the roles of PTKs in undifferentiated and differentiated hESCs. To establish a comprehensive PTK expression profiles in hESCs, we performed reverse transcriptase-PCR using degenerate primers according to the conserved catalytic PTK motifs in both undifferentiated and differentiated hESCs. Here, we identified 42 different kinases in two hESC lines, including 5 non-receptor tyrosine kinases, 24 receptor tyrosine kinases, and 13 dual and other kinases, and compared the protein kinase expression profiles of hESCs and RA-treated hESCs. Significantly up- and downregulated kinases in undifferentiated hESCs were confirmed by real-time PCR and western blotting. MAP3K3, ERBB2, FGFR4, and EPHB2 were predominantly upregulated, while CSF1R, TYRO3, SRC, and GSK3A were consistently downregulated in two hESC lines. Western blot analysis showed that the transcriptional levels of these kinases were consistent with translational levels. The obstruction of upregulated kinases activities using specific inhibitors disturbed undifferentiated status and induced differentiation of hESCs. Our results support the dynamic expression of PTKs during hESC maintenance and suggest that specific PTKs that are consistently up- and downregulated play important roles in the maintenance of stemness and the direction of differentiation of hESCs.