Home LiteratureArticle Details
PMID: 21183079 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A tissue-specific atlas of mouse protein phosphorylation and expression.

Cell ·Vol. 143 ·No. 7 ·2010-12-23 ·Pages 1174-89

Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villén J, Haas W, Sowa ME, Gygi SP

Abstract

Although most tissues in an organism are genetically identical, the biochemistry of each is optimized to fulfill its unique physiological roles, with important consequences for human health and disease. Each tissue's unique physiology requires tightly regulated gene and protein expression coordinated by specialized, phosphorylation-dependent intracellular signaling. To better understand the role of phosphorylation in maintenance of physiological differences among tissues, we performed proteomic and phosphoproteomic characterizations of nine mouse tissues. We identified 12,039 proteins, including 6296 phosphoproteins harboring nearly 36,000 phosphorylation sites. Comparing protein abundances and phosphorylation levels revealed specialized, interconnected phosphorylation networks within each tissue while suggesting that many proteins are regulated by phosphorylation independently of their expression. Our data suggest that the "typical" phosphoprotein is widely expressed yet displays variable, often tissue-specific phosphorylation that tunes protein activity to the specific needs of each tissue. We offer this dataset as an online resource for the biological research community.

MeSH Terms
Animals Gene Expression Profiling Mice/genetics,metabolism Organ Specificity Phosphorylation Protein Kinases/genetics Proteins/metabolism Proteomics
Chemicals
Proteins Protein Kinases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Huttlin Edward L
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Jedrychowski Mark P
Elias Joshua E
Goswami Tapasree
Rad Ramin
Beausoleil Sean A
Villén Judit
Haas Wilhelm
Sowa Mathew E
Gygi Steven P
References (48)
48 references, click to expand
  1. Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry.
    Nat Methods. 2007 Mar;4(3):207-14 PMID: 17327847
  2. Autoactivation of catalytic (C alpha) subunit of cyclic AMP-dependent protein kinase by phosphorylation of threonine 197.
    Mol Cell Biol. 1993 Apr;13(4):2332-41 PMID: 8455615
  3. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
    Sci Signal. 2010 Jan 12;3(104):ra3 PMID: 20068231
  4. Protein secondary structure prediction based on position-specific scoring matrices.
    J Mol Biol. 1999 Sep 17;292(2):195-202 PMID: 10493868
  5. The SCX/IMAC enrichment approach for global phosphorylation analysis by mass spectrometry.
    Nat Protoc. 2008;3(10):1630-8 PMID: 18833199
  6. Differential expression of spleen tyrosine kinase Syk isoforms in tissues: Effects of the microbial flora.
    Histochem Cell Biol. 2006 Oct;126(4):495-505 PMID: 16708245
  7. The Protein Information Resource.
    Nucleic Acids Res. 2003 Jan 1;31(1):345-7 PMID: 12520019
  8. Glycogen synthase kinase 3: a key regulator of cellular fate.
    Cell Mol Life Sci. 2007 Aug;64(15):1930-44 PMID: 17530463
  9. Deep coverage mouse red blood cell proteome: a first comparison with the human red blood cell.
    Mol Cell Proteomics. 2008 Jul;7(7):1317-30 PMID: 18344233
  10. Comparative proteomic phenotyping of cell lines and primary cells to assess preservation of cell type-specific functions.
    Mol Cell Proteomics. 2009 Mar;8(3):443-50 PMID: 18952599
  11. Linear motif atlas for phosphorylation-dependent signaling.
    Sci Signal. 2008 Sep 02;1(35):ra2 PMID: 18765831
  12. The human disease network.
    Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90 PMID: 17502601
  13. Predicting protein post-translational modifications using meta-analysis of proteome scale data sets.
    Mol Cell Proteomics. 2009 Feb;8(2):365-79 PMID: 18974045
  14. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.
    J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89 PMID: 24226387
  15. Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling.
    Cell. 2006 Apr 7;125(1):173-86 PMID: 16615898
  16. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.
    EMBO J. 2004 Feb 25;23(4):833-43 PMID: 14976552
  17. Inhibition of unwanted proteolysis during sample preparation: evaluation of its efficiency in challenge experiments.
    Electrophoresis. 2002 Jun;23(11):1745-53 PMID: 12179996
  18. The MAP2/Tau family of microtubule-associated proteins.
    Genome Biol. 2005;6(1):204 PMID: 15642108
  19. A gene atlas of the mouse and human protein-encoding transcriptomes.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7 PMID: 15075390
  20. Large-scale phosphorylation analysis of mouse liver.
    Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1488-93 PMID: 17242355
  21. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase.
    Science. 2006 May 5;312(5774):734-7 PMID: 16675698
  22. Brain phosphoproteome obtained by a FASP-based method reveals plasma membrane protein topology.
    J Proteome Res. 2010 Jun 4;9(6):3280-9 PMID: 20415495
  23. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  24. PhosphoSite: A bioinformatics resource dedicated to physiological protein phosphorylation.
    Proteomics. 2004 Jun;4(6):1551-61 PMID: 15174125
  25. KEGG for representation and analysis of molecular networks involving diseases and drugs.
    Nucleic Acids Res. 2010 Jan;38(Database issue):D355-60 PMID: 19880382
  26. Phosphorylation states of microtubule-associated protein 2 (MAP2) determine the regulatory role of MAP2 in microtubule dynamics.
    Biochemistry. 1997 Oct 14;36(41):12574-82 PMID: 9376363
  27. Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes.
    J Biol Chem. 2007 Jan 12;282(2):996-1002 PMID: 17114792
  28. DAVID: Database for Annotation, Visualization, and Integrated Discovery.
    Genome Biol. 2003;4(5):P3 PMID: 12734009
  29. Structure and regulation of MARK, a kinase involved in abnormal phosphorylation of Tau protein.
    BMC Neurosci. 2008 Dec 03;9 Suppl 2:S9 PMID: 19090997
  30. Connecdenn, a novel DENN domain-containing protein of neuronal clathrin-coated vesicles functioning in synaptic vesicle endocytosis.
    J Neurosci. 2006 Dec 20;26(51):13202-12 PMID: 17182770
  31. Regulation and function of triacylglycerol lipases in cellular metabolism.
    Biochem J. 2008 Sep 15;414(3):313-25 PMID: 18717647
  32. The MAP1 family of microtubule-associated proteins.
    Genome Biol. 2006;7(6):224 PMID: 16938900
  33. Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in the regulatory loop and inhibits microtubule affinity-regulating kinase (MARK) 2.
    J Biol Chem. 2008 Jul 4;283(27):18873-82 PMID: 18424437
  34. A global map of human gene expression.
    Nat Biotechnol. 2010 Apr;28(4):322-4 PMID: 20379172
  35. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
    Cell. 2006 Nov 3;127(3):635-48 PMID: 17081983
  36. A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
    Nat Biotechnol. 2006 Oct;24(10):1285-92 PMID: 16964243
  37. A model for random sampling and estimation of relative protein abundance in shotgun proteomics.
    Anal Chem. 2004 Jul 15;76(14):4193-201 PMID: 15253663
  38. Phospho.ELM: a database of phosphorylation sites--update 2008.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D240-4 PMID: 17962309
  39. Length-dependent prediction of protein intrinsic disorder.
    BMC Bioinformatics. 2006 Apr 17;7:208 PMID: 16618368
  40. MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1.
    EMBO J. 2003 Oct 1;22(19):5090-101 PMID: 14517247
  41. A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth.
    Nat Neurosci. 2002 May;5(5):431-7 PMID: 11976703
  42. Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs.
    Nucleic Acids Res. 2003 Jul 1;31(13):3635-41 PMID: 12824383
  43. BAD: undertaker by night, candyman by day.
    Oncogene. 2008 Dec;27 Suppl 1:S53-70 PMID: 19641507
  44. Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns.
    Anal Chem. 2004 Jul 15;76(14):3935-43 PMID: 15253627
  45. Non-functional phosphorylations?
    Trends Biochem Sci. 2008 Aug;33(8):351-2 PMID: 18603430
  46. Syk tyrosine kinase participates in beta1-integrin signaling and inflammatory responses in airway epithelial cells.
    Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L497-507 PMID: 15557085
  47. SNARE-mediated membrane fusion.
    Nat Rev Mol Cell Biol. 2001 Feb;2(2):98-106 PMID: 11252968
  48. STRING 8--a global view on proteins and their functional interactions in 630 organisms.
    Nucleic Acids Res. 2009 Jan;37(Database issue):D412-6 PMID: 18940858
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
Published
2010-12-23
Pages
1174-89
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3035969
Subset
IM
Grants
NHGRI NIH HHS · R01 HG003456 · United States
NHGRI NIH HHS · R01 HG003456-06 · United States
NHGRI NIH HHS · HG3456 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com