Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation
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Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation. / Emdal, Kristina B; Pedersen, Anna-Kathrine; Bekker-Jensen, Dorte B; Tsafou, Kalliopi P; Horn, Heiko; Lindner, Sven; Schulte, Johannes H; Eggert, Angelika; Jensen, Lars Juhl; Francavilla, Chiara; Olsen, Jesper V.
In: Science Signaling, Vol. 8, No. 374, ra40, 2015.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation
AU - Emdal, Kristina B
AU - Pedersen, Anna-Kathrine
AU - Bekker-Jensen, Dorte B
AU - Tsafou, Kalliopi P
AU - Horn, Heiko
AU - Lindner, Sven
AU - Schulte, Johannes H
AU - Eggert, Angelika
AU - Jensen, Lars Juhl
AU - Francavilla, Chiara
AU - Olsen, Jesper V
N1 - Copyright © 2015, American Association for the Advancement of Science.
PY - 2015
Y1 - 2015
N2 - SH-SY5Y neuroblastoma cells respond to nerve growth factor (NGF)-mediated activation of the tropomyosin-related kinase A (TrkA) with neurite outgrowth, thereby providing a model to study neuronal differentiation. We performed a time-resolved analysis of NGF-TrkA signaling in neuroblastoma cells using mass spectrometry-based quantitative proteomics. The combination of interactome, phosphoproteome, and proteome data provided temporal insights into the molecular events downstream of NGF binding to TrkA. We showed that upon NGF stimulation, TrkA recruits the E3 ubiquitin ligase Cbl-b, which then becomes phosphorylated and ubiquitylated and decreases in abundance. We also found that recruitment of Cbl-b promotes TrkA ubiquitylation and degradation. Furthermore, the amount of phosphorylation of the kinase ERK and neurite outgrowth increased upon Cbl-b depletion in several neuroblastoma cell lines. Our findings suggest that Cbl-b limits NGF-TrkA signaling to control the length of neurites.
AB - SH-SY5Y neuroblastoma cells respond to nerve growth factor (NGF)-mediated activation of the tropomyosin-related kinase A (TrkA) with neurite outgrowth, thereby providing a model to study neuronal differentiation. We performed a time-resolved analysis of NGF-TrkA signaling in neuroblastoma cells using mass spectrometry-based quantitative proteomics. The combination of interactome, phosphoproteome, and proteome data provided temporal insights into the molecular events downstream of NGF binding to TrkA. We showed that upon NGF stimulation, TrkA recruits the E3 ubiquitin ligase Cbl-b, which then becomes phosphorylated and ubiquitylated and decreases in abundance. We also found that recruitment of Cbl-b promotes TrkA ubiquitylation and degradation. Furthermore, the amount of phosphorylation of the kinase ERK and neurite outgrowth increased upon Cbl-b depletion in several neuroblastoma cell lines. Our findings suggest that Cbl-b limits NGF-TrkA signaling to control the length of neurites.
U2 - 10.1126/scisignal.2005769
DO - 10.1126/scisignal.2005769
M3 - Journal article
C2 - 25921289
VL - 8
JO - Science Signaling
JF - Science Signaling
SN - 1945-0877
IS - 374
M1 - ra40
ER -
ID: 137983377