The Scripps Research Institute, 현 Rutgers University



Laurence M. Brill1, 2, 5, *, Wen Xiong3, 5, Ki-Bum Lee3, 5, 6, Scott B. Ficarro1, 7, Andrew Crain2, 4, Yue Xu3, Alexey Terskikh2, Evan Y. Snyder2, *, Sheng Ding3, *

1 Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92109, USA
2 Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
3 Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
4 Biomedical Sciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
5 These authors contributed equally to this work
6 Present address: Department of Chemistry and Chemical Biology, Institute for Advanced Materials, Devices, and Nanotechnology, The Rutgers Stem Cell Research Center, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854, USA
7 Present address: Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA

*Corresponding author : Laurence M. Brill, Evan Y. Snyder, Sheng Ding

Protein phosphorylation, while critical to cellular behavior, has been undercharacterized in pluripotent cells. Therefore, we performed phosphoproteomic analyses of human embryonic stem cells (hESCs) and their differentiated derivatives. A total of 2546 phosphorylation sites were identified on 1602 phosphoproteins; 389 proteins contained more phosphorylation site identifications in undifferentiated hESCs, whereas 540 contained more such identifications in differentiated derivatives. Phosphoproteins in receptor tyrosine kinase (RTK) signaling pathways were numerous in undifferentiated hESCs. Cellular assays corroborated this observation by showing that multiple RTKs cooperatively supported undifferentiated hESCs. In addition to bFGF, EGFR, VEGFR, and PDGFR activation was critical to the undifferentiated state of hESCs. PDGF-AA complemented a subthreshold bFGF concentration to maintain undifferentiated hESCs. Also consistent with phosphoproteomics, JNK activity participated in maintenance of undifferentiated hESCs. These results support the utility of phosphoproteomic data, provide guidance for investigating protein function in hESCs, and complement transcriptomics/epigenetics for broadening our understanding of hESC fate determination.


- 형식: Research article
- 게재일: 2009년 08월 (BRIC 등록일 2011-03-11)
- 연구진: 국외연구진
- 분야: Cell_Biology
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