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Identification of ABL Kinase Substrates by Kinase Assay Linked Phosphoproteomics and Multiple Drug Treatments

ABSTRACT: The kinase assay linked phosphoproteomics (KALIP) strategy was used to identify direct substrates of the Abelson tyrosine kinase (ABL). First, kinase assays using peptides and proteins from chronic myelogenous leukemia cells and recombinant ABL were done to identify kinase substrates in vitro. The ABL-dependent endogenous phosphoproteome was also examined using multiple drug treatments (imatinib, dasatinib, and bosutinib versus a vehicle treated control) and label-free quantitation after LC-MS/MS. The in vitro and in vivo substrate candidates were then compared to produce a list of highly confident direct ABL substrates.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: W. Andy Tao

PROVIDER: PXD005431 | JPOST Repository | Wed Mar 20 00:00:00 GMT 2019

REPOSITORIES: jPOST

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			Action	DRS
	051213-Dasat-PolyMAC.raw	Raw
	051213-Imat-PolyMAC.raw	Raw
	051313-Bosut-PolyMAC.raw	Raw
	051313-NoTKI-PolyMAC.raw	Raw
	052513-Bosut-PolyMAC.raw	Raw

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Publications

Identification of the Direct Substrates of the ABL Kinase via Kinase Assay Linked Phosphoproteomics with Multiple Drug Treatments.

Arrington Justine J Xue Liang L Wang Wen-Horng WH Geahlen Robert L RL Tao W Andy WA

Journal of proteome research 20190321 4

Ableson tyrosine kinase (ABL) plays essential roles in cell differentiation, division, adhesion, and stress response. However, fusion of the breakpoint cluster region (BCR) to ABL produces constitutive kinase activity that causes chronic myelogenous leukemia (CML). Small molecule tyrosine kinase inhibitors (TKIs) such as imatinib revolutionized the treatment of CML and other cancers, but acquired resistance to these inhibitors is rising. Thus, careful dissection of ABL signaling pathways is need ...[more]

PMID: 30869898

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