Phosphorylation dynamics during early differentiation of human embryonic stem cells - PubMed

Affiliations

• PMID: 19664995
• DOI: 10.1016/j.stem.2009.05.021

Free article

Phosphorylation dynamics during early differentiation of human embryonic stem cells

Dennis Van Hoof et al. Cell Stem Cell. 2009.

Free article

Abstract

Pluripotent stem cells self-renew indefinitely and possess characteristic protein-protein networks that remodel during differentiation. How this occurs is poorly understood. Using quantitative mass spectrometry, we analyzed the (phospho)proteome of human embryonic stem cells (hESCs) during differentiation induced by bone morphogenetic protein (BMP) and removal of hESC growth factors. Of 5222 proteins identified, 1399 were phosphorylated on 3067 residues. Approximately 50% of these phosphosites were regulated within 1 hr of differentiation induction, revealing a complex interplay of phosphorylation networks spanning different signaling pathways and kinase activities. Among the phosphorylated proteins was the pluripotency-associated protein SOX2, which was SUMOylated as a result of phosphorylation. Using the data to predict kinase-substrate relationships, we reconstructed the hESC kinome; CDK1/2 emerged as central in controlling self-renewal and lineage specification. The findings provide new insights into how hESCs exit the pluripotent state and present the hESC (phospho)proteome resource as a complement to existing pluripotency network databases.

Comment in

• Unraveling the human embryonic stem cell phosphoproteome.

  Hutchins AP, Robson P. Hutchins AP, et al. Cell Stem Cell. 2009 Aug 7;5(2):126-8. doi: 10.1016/j.stem.2009.07.007. Cell Stem Cell. 2009. PMID: 19664982

Similar articles

• Quantitative proteome and phosphoproteome analysis of human pluripotent stem cells.

  Muñoz J, Heck AJ. Muñoz J, et al. Methods Mol Biol. 2011;767:297-312. doi: 10.1007/978-1-61779-201-4_22. Methods Mol Biol. 2011. PMID: 21822884

• Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells.

  Xiao L, Yuan X, Sharkis SJ. Xiao L, et al. Stem Cells. 2006 Jun;24(6):1476-86. doi: 10.1634/stemcells.2005-0299. Epub 2006 Feb 2. Stem Cells. 2006. PMID: 16456129

• The role of nuclear receptors in embryonic stem cells.

  Wang Q, Cooney AJ. Wang Q, et al. Adv Exp Med Biol. 2013;786:287-306. doi: 10.1007/978-94-007-6621-1_16. Adv Exp Med Biol. 2013. PMID: 23696363 Review.

• Signaling roadmap modulating naive and primed pluripotency.

  Hassani SN, Totonchi M, Gourabi H, Schöler HR, Baharvand H. Hassani SN, et al. Stem Cells Dev. 2014 Feb 1;23(3):193-208. doi: 10.1089/scd.2013.0368. Epub 2013 Nov 27. Stem Cells Dev. 2014. PMID: 24147644 Review.

Cited by

• Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma.

  Gelebart P, Hegazy SA, Wang P, Bone KM, Anand M, Sharon D, Hitt M, Pearson JD, Ingham RJ, Ma Y, Lai R. Gelebart P, et al. Blood Cancer J. 2012 Aug 10;2(8):e82. doi: 10.1038/bcj.2012.27. Blood Cancer J. 2012. PMID: 22885405 Free PMC article.

• PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.

  Yuan Y, Wang C, Zhuang X, Lin S, Luo M, Deng W, Zhou J, Liu L, Mao L, Peng W, Chen J, Wang Q, Shu Y, Xue Y, Huang P. Yuan Y, et al. Nat Commun. 2022 Sep 6;13(1):5237. doi: 10.1038/s41467-022-32976-9. Nat Commun. 2022. PMID: 36068222 Free PMC article.

• Snapshots of kinase activities.

  Muñoz J, Heck AJ. Muñoz J, et al. Nat Biotechnol. 2009 Oct;27(10):912-3. doi: 10.1038/nbt1009-912. Nat Biotechnol. 2009. PMID: 19816446 No abstract available.

• Sox2 uses multiple domains to associate with proteins present in Sox2-protein complexes.

  Cox JL, Mallanna SK, Luo X, Rizzino A. Cox JL, et al. PLoS One. 2010 Nov 12;5(11):e15486. doi: 10.1371/journal.pone.0015486. PLoS One. 2010. PMID: 21103394 Free PMC article.

• Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction.

  Wang Y, Yang F, Fu Y, Huang X, Wang W, Jiang X, Gritsenko MA, Zhao R, Monore ME, Pertz OC, Purvine SO, Orton DJ, Jacobs JM, Camp DG 2nd, Smith RD, Klemke RL. Wang Y, et al. J Biol Chem. 2011 May 20;286(20):18190-201. doi: 10.1074/jbc.M111.236133. Epub 2011 Mar 28. J Biol Chem. 2011. PMID: 21454597 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • GlyGen glycoinformatics resource
  • PhosphoSitePlus

• Miscellaneous

  • NCI CPTAC Assay Portal