TY - JOUR
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
N1 - MEDLINE® is the source for the MeSH terms of this document.
PY - 2005/12/1
Y1 - 2005/12/1
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.
UR - http://www.scopus.com/inward/record.url?scp=28444460297&partnerID=8YFLogxK
U2 - 10.1038/nature04187
DO - 10.1038/nature04187
M3 - Letter
C2 - 16319894
SN - 1476-4687
VL - 438
SP - 679
EP - 684
JO - Nature
JF - Nature
IS - 7068
ER -