PXD025896

PXD025896 is an original dataset announced via ProteomeXchange.

Title	Identification of phosphorylation sites on Abl2
Description	The catalytic activity of Abl family kinases is tightly regulated in cells by a complex set of intra- and intermolecular interactions and post-translational modifications. Abl family kinases are activated by diverse cellular stimuli, one of them being receptor tyrosine kinase signaling. For example, platelet-derived growth factor receptor beta (PDGFRβ) has been identified as a potent activator of Abl family kinases. However, the molecular mechanism by which PDGFRβ engages and activates Abl family kinases is not known. We report here the molecular mechanism by which PDGFRβ interacts, phosphorylates and activates Abl2 kinase. We found that PDGFRβ binds and phosphorylates Abl2 both in vitro and in cells. We also identified several novel PDGFRβ phosphorylation sites on Abl2, including Y116, Y139 and Y161 on the SH3 domain, and Y299, Y303 and Y310 on the kinase domain. Of notable interest, Y116, Y161, Y272 and Y310 are all located near the SH3/SH2-kinase linker interface, which help maintain Abl family kinases in an auto-inhibited conformation. Mutation of these four tyrosine (Y116, Y161, Y272 and Y310) to phenylalanine abrogated PDGFRβ-mediated activation of Abl2 kinase activity. These findings provide a mechanism to understand how receptor tyrosine kinases activate Abl family kinases, and how Abl kinases are precisely regulated through different phosphorylation events.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_03:29:53.322.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025896
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jingyun Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-09 07:49:57	ID requested
⏵ 1	2022-02-17 03:29:54	announced

Wu K, Wu H, Lyu W, Kim Y, Furdui CM, Anderson KS, Koleske AJ, Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation. J Biol Chem, 297(1):100883(2021) [pubmed]

submitter keyword: Abl2, PDGFR-beta, human

Cristina M. Furdui
contact affiliation	Department of Internal Medicine, Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States
contact email	cfurdui@wakehealth.edu
lab head
Jingyun Lee
contact affiliation	Wake Forest Baptist Health
contact email	jilee@wakehealth.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025896
     1. Label: PRIDE project
     2. Name: Identification of phosphorylation sites on Abl2