Stable and EGF-Induced Temporal Interactome Profiling of CBL and CBLB Highlights Their Signaling Complex Diversity

Liu, Jie1,2; Yang, Lijun1,2; He, An3; Ke, Mi3; Fu, Changying4; Gao, Weina3; Xu, Ruilian1,2; Tian, Ruijun3

2021-07-02

10.1021/acs.jproteome.1c00284

JOURNAL OF PROTEOME RESEARCH   影响因子和分区

1535-3893

1535-3907

The epidermal growth factor receptor (EGFR) signal modulates cell proliferation, migration, and survival. Aberrant activation of EGFR constitutes the major cause of various cancers. Receptor ubiquitination and degradation mediated by CBL proteins play negative regulatory roles and control the intensity and duration of the signaling. With the construction of stable cell lines inducibly expressing FLAG-tagged CBL or CBLB, we identified 102 and 82 stable interacting proteins of CBL and CBLB, respectively, through the affinity purification followed by mass spectrometry (AP-MS) approach. Time-resolved profiling at six different time points combined with functional annotations of the temporal interactomes provides insights into the dynamic assembly of signal proteins upon EGFR signaling activation. Comparison between the interactomes of CBL and CBLB indicates their redundant but also complementary functions. Importantly, we validated the stable association of EPS15L1 and ITSN2 and temporal association of TNK2 to both CBL and CBLB through biochemical assays. Collectively, these results offer a useful resource for CBL and CBLB interactomes and highlight their prominent and diverse roles in the EGFR signaling network.

APMS signal transduction CBL CBLB dynamic protein complexes

SCI

英语

通讯

National Natural Science Foundation of China[22004049,31700088] ; China Postdoctoral Science Foundation[2020M683168] ; China State Key Basic Research Program["2020YFE0202200","2016YFA0501403","2016YFA0501404"] ; Guangdong Provincial Fund for Distinguished Young Scholars[2019B151502050] ; Shenzhen Innovation of Science and Technology Commission["JCYJ20200109141212325","JCYJ20170412154126026"] ; SUSTech grant[G02216304/G02216404]

Biochemistry & Molecular Biology

Biochemical Research Methods

WOS:000670662100029

AMER CHEMICAL SOC

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Jinan Univ, Clin Med Coll 2, Dept Oncol, Shenzhen Peoples Hosp, Shenzhen 518020, Peoples R China
2.Jinan Univ, Affiliated Hosp 1, Guangzhou 510632, Peoples R China
3.Southern Univ Sci & Technol, Coll Sci, Dept Chem, Shenzhen 518055, Peoples R China
4.Southern Univ Sci & Technol, Acad Adv Interdisciplinary Studies, Shenzhen 518055, Peoples R China

Liu, Jie,Yang, Lijun,He, An,et al. Stable and EGF-Induced Temporal Interactome Profiling of CBL and CBLB Highlights Their Signaling Complex Diversity[J]. JOURNAL OF PROTEOME RESEARCH,2021,20(7).

Liu, Jie.,Yang, Lijun.,He, An.,Ke, Mi.,Fu, Changying.,...&Tian, Ruijun.(2021).Stable and EGF-Induced Temporal Interactome Profiling of CBL and CBLB Highlights Their Signaling Complex Diversity.JOURNAL OF PROTEOME RESEARCH,20(7).

Liu, Jie,et al."Stable and EGF-Induced Temporal Interactome Profiling of CBL and CBLB Highlights Their Signaling Complex Diversity".JOURNAL OF PROTEOME RESEARCH 20.7(2021).