What does this research mean for the field?

The c-Cbl protein functions as an E3 ubiquitin-protein ligase that recognizes tyrosine-phosphorylated substrates via its SH2 domain and recruits and activates an E2 ubiquitin-conjugating enzyme via its RING domain. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.ESTABLISHES_NEW_DIRECTION.

What question did this study set out to answer?

To determine whether and how the negative regulator c-Cbl functions directly as an E3 ubiquitin-protein ligase to terminate receptor protein-tyrosine kinase signaling.

October 8, 1999Science

The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase

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Authors

CJClaudio A.P. JoazeiroScripps Research Institute SWSimon S. WingMcGill University Health Centre HHHan-kuei HuangSalk Institute for Biological Studies

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Implication

Experimental molecular study reveals that c-Cbl acts as a RING-type ubiquitin ligase targeting activated receptor tyrosine kinases, uncovering a distinct mechanism for substrate degradation.

Key Points

To determine whether and how the negative regulator c-Cbl functions directly as an E3 ubiquitin-protein ligase to terminate receptor protein-tyrosine kinase signaling.
Assessed the biochemical activity of c-Cbl and the specific roles of its variant SRC homology 2 (SH2) and RING finger domains.
Investigated domain-dependent interactions with E2 ubiquitin-conjugating enzymes and phosphorylated target substrates, including the activated platelet-derived growth factor receptor.
c-Cbl functions directly as an E3 ubiquitin-protein ligase that recruits and allosterically activates an E2 ubiquitin-conjugating enzyme via its RING finger domain.
The variant SH2 domain of c-Cbl selectively recognizes tyrosine-phosphorylated substrates to direct their ubiquitination and promote receptor degradation.

Cite This Study

Joazeiro et al. (1999) studied this question.

synapsesocial.com/papers/6a0d32b136162e2f4b09a77b https://doi.org/10.1126/science.286.5438.309

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Implication

Experimental molecular study reveals that c-Cbl acts as a RING-type ubiquitin ligase targeting activated receptor tyrosine kinases, uncovering a distinct mechanism for substrate degradation.

The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase

Discussion

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Implication

Key Points

Cite This Study

The Tyrosine Kinase Negative Regulator c-Cbl as a RING-Type, E2-Dependent Ubiquitin-Protein Ligase

Discussion

Member takes

Implication

Key Points

Cite This Study

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