The Ubiquitin Ligases c-Cbl and Cbl-b Negatively Regulate Platelet-derived Growth Factor (PDGF) BB-induced Chemotaxis by Affecting PDGF Receptor β (PDGFRβ) Internalization and Signaling

Rorsman, Charlotte; Tsioumpekou, Maria; Heldin, Carl‐Henrik; Lennartsson, Johan

doi:10.1074/jbc.m115.705814

Cited by 35 publications

(25 citation statements)

References 26 publications

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“…Congruent with the role played by ubiquitin in signal transduction, endosome sorting, and protein degradation, when the CBL and CBLB signalosomes were subjected to GO term enrichment analysis (Bindea et al , ), a significant overrepresentation of annotations related to “signaling adaptor activity” and “role in protein degradation” was observed (Fig EV3). In line with studies performed in adipocytes and fibroblasts and suggesting that CBL and CBLB are capable of heterodimerizing (Liu et al , ; Rorsman et al , ), CBLB was found in the CBL signalosome (Fig D). The lower cellular abundance of CBLB as compared to CBL (Fig B) and the detection limit achieved in our AP‐MS experiments might explain why no CBL‐specific peptide was recovered from the CBLB signalosome (Fig C).…”

Section: Resultssupporting

confidence: 90%

“…In line with studies performed in adipocytes and fibroblasts and suggesting that CBL and CBLB are capable of heterodimerizing (Liu et al, 2003;Rorsman et al, 2016), CBLB was found in the CBL signalosome ( Fig 2D). The lower cellular abundance of CBLB as compared to CBL ( Fig 1B) and the detection limit achieved in our AP-MS experiments might explain why no CBL-specific peptide was recovered from the CBLB signalosome ( Fig 2C).…”

Section: Molecular Systems Biologysupporting

confidence: 90%

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Co‐recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD 5 as a key regulator of TCR ‐induced ubiquitylation

Voisinne

García-Blesa

Chaoui

et al. 2016

Molecular Systems Biology

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T‐cell receptor (TCR) signaling is essential for the function of T cells and negatively regulated by the E3 ubiquitin–protein ligases CBL and CBLB. Here, we combined mouse genetics and affinity purification coupled to quantitative mass spectrometry to monitor the dynamics of the CBL and CBLB signaling complexes that assemble in normal T cells over 600 seconds of TCR stimulation. We identify most previously known CBL and CBLB interacting partners, as well as a majority of proteins that have not yet been implicated in those signaling complexes. We exploit correlations in protein association with CBL and CBLB as a function of time of TCR stimulation for predicting the occurrence of direct physical association between them. By combining co‐recruitment analysis with biochemical analysis, we demonstrated that the CD5 transmembrane receptor constitutes a key scaffold for CBL‐ and CBLB‐mediated ubiquitylation following TCR engagement. Our results offer an integrated view of the CBL and CBLB signaling complexes induced by TCR stimulation and provide a molecular basis for their negative regulatory function in normal T cells.

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Section: Resultssupporting

confidence: 90%

Section: Molecular Systems Biologysupporting

confidence: 90%

Co‐recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD 5 as a key regulator of TCR ‐induced ubiquitylation

Voisinne

García-Blesa

Chaoui

et al. 2016

Molecular Systems Biology

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“…The here reported HCV host factor CBLB is an E3-ubiquitin ligase, which functions together with CBL [42]. CBLB and CBL regulate EGFR endocytosis by ubiquitination of the cytosolic receptor domains [43,44].…”

Section: The Cd81 Network Protein Cblb As Virus Entry Facilitatormentioning

confidence: 79%

Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

et al. 2018

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Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.

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“…[18,19]. Regranex gel dilutions in media has been tested in cell culture and the concentration below 10 μg (0.001%) did not show any significant response in our experiments [20]. …”

Section: Methodsmentioning

confidence: 96%

Rapid tissue regeneration induced by intracellular ATP delivery—A preliminary mechanistic study

et al. 2017

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We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery—extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold promise for acute and chronic wound care.

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The Ubiquitin Ligases c-Cbl and Cbl-b Negatively Regulate Platelet-derived Growth Factor (PDGF) BB-induced Chemotaxis by Affecting PDGF Receptor β (PDGFRβ) Internalization and Signaling

Cited by 35 publications

References 26 publications

Co‐recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD 5 as a key regulator of TCR ‐induced ubiquitylation

Co‐recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD 5 as a key regulator of TCR ‐induced ubiquitylation

Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

Rapid tissue regeneration induced by intracellular ATP delivery—A preliminary mechanistic study

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