Proteomics

Dataset Information

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Identification of phosphorylation sites on Abl2


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Disease Free

SUBMITTER: Jingyun Lee  

LAB HEAD: Cristina M. Furdui

PROVIDER: PXD025896 | Pride | 2022-02-17

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Abl2N_phos_01_TiO2.msf Msf
Abl2N_phos_01_TiO2.mzML Mzml
Abl2N_phos_01_TiO2.mzid.gz Mzid
Abl2N_phos_01_TiO2.raw Raw
Abl2N_phos_02_TiO2.msf Msf
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Publications

Platelet-derived growth factor receptor beta activates Abl2 via direct binding and phosphorylation.

Wu Kuanlin K   Wu Hanzhi H   Lyu Wanqing W   Kim Youngjoo Y   Furdui Cristina M CM   Anderson Karen S KS   Koleske Anthony J AJ  

The Journal of biological chemistry 20210616 1


Abl family kinases are nonreceptor tyrosine kinases activated by diverse cellular stimuli that regulate cytoskeleton organization, morphogenesis, and adhesion. The catalytic activity of Abl family kinases is tightly regulated in cells by a complex set of intramolecular and intermolecular interactions and post-translational modifications. For example, the platelet-derived growth factor receptor beta (PDGFRβ), important for cell proliferation and chemotaxis, is a potent activator of Abl family kin  ...[more]

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