Global analysis of protein phosphorylation in yeast

Jason Ptacek, Geeta Devgan, Gregory Michaud, Heng Zhu, Xiaowei Zhu, Joseph Fasolo, Hong Guo, Ghil Jona, Ashton Breitkreutz, Richelle Sopko, Rhonda R. McCartney, Martin C. Schmidt, Najma Rachidi, Soo-Jung Lee, Angie S. Mah, Lihao Meng, Michael J. R. Stark, David F. Stern, Claudio De Virgilio, Mike TyersBrenda Andrews, Mark Gerstein, Barry Schweitzer, Paul F. Predki, Michael Snyder

    Research output: Contribution to journalLetter

    745 Citations (Scopus)

    Abstract

    Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.
    Original languageEnglish
    Pages (from-to)679-684
    Number of pages6
    JournalNature
    Volume438
    Issue number7068
    DOIs
    Publication statusPublished - 1 Dec 2005

    Fingerprint

    Yeasts
    Phosphorylation
    Phosphotransferases
    Proteins
    Fungal Proteins
    Proteome
    Protein Kinases
    Cyclins
    Cyclin-Dependent Kinases
    Phosphoproteins
    Cyclic AMP-Dependent Protein Kinases
    Eukaryota
    Transcription Factors
    Technology

    Cite this

    Ptacek, J., Devgan, G., Michaud, G., Zhu, H., Zhu, X., Fasolo, J., ... Snyder, M. (2005). Global analysis of protein phosphorylation in yeast. Nature, 438(7068), 679-684. https://doi.org/10.1038/nature04187
    Ptacek, Jason ; Devgan, Geeta ; Michaud, Gregory ; Zhu, Heng ; Zhu, Xiaowei ; Fasolo, Joseph ; Guo, Hong ; Jona, Ghil ; Breitkreutz, Ashton ; Sopko, Richelle ; McCartney, Rhonda R. ; Schmidt, Martin C. ; Rachidi, Najma ; Lee, Soo-Jung ; Mah, Angie S. ; Meng, Lihao ; Stark, Michael J. R. ; Stern, David F. ; De Virgilio, Claudio ; Tyers, Mike ; Andrews, Brenda ; Gerstein, Mark ; Schweitzer, Barry ; Predki, Paul F. ; Snyder, Michael. / Global analysis of protein phosphorylation in yeast. In: Nature. 2005 ; Vol. 438, No. 7068. pp. 679-684.
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    abstract = "Protein phosphorylation is estimated to affect 30{\%} of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.",
    author = "Jason Ptacek and Geeta Devgan and Gregory Michaud and Heng Zhu and Xiaowei Zhu and Joseph Fasolo and Hong Guo and Ghil Jona and Ashton Breitkreutz and Richelle Sopko and McCartney, {Rhonda R.} and Schmidt, {Martin C.} and Najma Rachidi and Soo-Jung Lee and Mah, {Angie S.} and Lihao Meng and Stark, {Michael J. R.} and Stern, {David F.} and {De Virgilio}, Claudio and Mike Tyers and Brenda Andrews and Mark Gerstein and Barry Schweitzer and Predki, {Paul F.} and Michael Snyder",
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    Ptacek, J, Devgan, G, Michaud, G, Zhu, H, Zhu, X, Fasolo, J, Guo, H, Jona, G, Breitkreutz, A, Sopko, R, McCartney, RR, Schmidt, MC, Rachidi, N, Lee, S-J, Mah, AS, Meng, L, Stark, MJR, Stern, DF, De Virgilio, C, Tyers, M, Andrews, B, Gerstein, M, Schweitzer, B, Predki, PF & Snyder, M 2005, 'Global analysis of protein phosphorylation in yeast', Nature, vol. 438, no. 7068, pp. 679-684. https://doi.org/10.1038/nature04187

    Global analysis of protein phosphorylation in yeast. / Ptacek, Jason; Devgan, Geeta; Michaud, Gregory; Zhu, Heng; Zhu, Xiaowei; Fasolo, Joseph; Guo, Hong; Jona, Ghil; Breitkreutz, Ashton; Sopko, Richelle; McCartney, Rhonda R.; Schmidt, Martin C.; Rachidi, Najma; Lee, Soo-Jung; Mah, Angie S.; Meng, Lihao; Stark, Michael J. R.; Stern, David F.; De Virgilio, Claudio; Tyers, Mike; Andrews, Brenda; Gerstein, Mark; Schweitzer, Barry; Predki, Paul F.; Snyder, Michael.

    In: Nature, Vol. 438, No. 7068, 01.12.2005, p. 679-684.

    Research output: Contribution to journalLetter

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    T1 - Global analysis of protein phosphorylation in yeast

    AU - Ptacek, Jason

    AU - Devgan, Geeta

    AU - Michaud, Gregory

    AU - Zhu, Heng

    AU - Zhu, Xiaowei

    AU - Fasolo, Joseph

    AU - Guo, Hong

    AU - Jona, Ghil

    AU - Breitkreutz, Ashton

    AU - Sopko, Richelle

    AU - McCartney, Rhonda R.

    AU - Schmidt, Martin C.

    AU - Rachidi, Najma

    AU - Lee, Soo-Jung

    AU - Mah, Angie S.

    AU - Meng, Lihao

    AU - Stark, Michael J. R.

    AU - Stern, David F.

    AU - De Virgilio, Claudio

    AU - Tyers, Mike

    AU - Andrews, Brenda

    AU - Gerstein, Mark

    AU - Schweitzer, Barry

    AU - Predki, Paul F.

    AU - Snyder, Michael

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    PY - 2005/12/1

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    N2 - Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

    AB - Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

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    Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J et al. Global analysis of protein phosphorylation in yeast. Nature. 2005 Dec 1;438(7068):679-684. https://doi.org/10.1038/nature04187