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Large-scale Discovery of Substrates of the Human Kinome

ABSTRACT: Kinase -networks are important for cellular signal transduction. Despite tremendous efforts to uncover these signaling pathways, huge numbers of uncharacterized phosphosites still remain in the human proteome. Because of the transient nature of kinase-substrate interactions in vivo, it is almost impossible to identify direct substrates. Here, we present a novel strategy for the rapid and high-throughput discovery for of kinase substrates of kinase using quantitative proteomics. Using 385 purified kinases, we identified a total of 175,574 potential direct kinase substrates of kinases. In addition, we identified novel kinase groups, such as one group containing 30 threonine-directed kinases and another containing 15 serine/threonine/tyrosine kinase sgroup. Surprisingly, we observed that the diversity of substrates for tyrosine kinases was much higher than that for serine-threonine kinases.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yasushi Ishihama

PROVIDER: PXD011366 | JPOST Repository | Mon Jul 22 00:00:00 BST 2019

REPOSITORIES: jPOST

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			Action	DRS
	mai100511_001EPHA1.RAW	Raw
	mai100511_002EPHB3.RAW	Raw
	mai100511_003LTK.RAW	Raw
	mai100511_004AXL.RAW	Raw
	mai100511_005TRKC_NTRK3.RAW	Raw

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Large-scale Discovery of Substrates of the Human Kinome.

Sugiyama Naoyuki N Imamura Haruna H Ishihama Yasushi Y

Scientific reports 20190719 1

Kinase networks are important for cellular signal transduction. Despite tremendous efforts to uncover these signaling pathways, huge numbers of uncharacterized phosphosites still remain in the human proteome. Because of the transient nature of kinase-substrate interactions in vivo, it is almost impossible to identify direct substrates. Here, we present a strategy for the rapid, accurate and high-throughput discovery of in vitro kinase substrates using quantitative proteomics. Using 385 purified ...[more]

PMID: 31324866

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