Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary structure of the receptor for platelet-derived growth factor (PDGF), determined by means of cloning a cDNA that encodes the murine pre-PDGF receptor, is closely related to that of the v-kit oncogene product and the receptor for macrophage colony stimulating factor (CSF-1). Common structural features include the presence of long sequences that interrupt the tyrosine-specific protein kinase domains of each molecule. The PDGF and CSF-1 receptors also share a characteristic distribution of extracellular cysteine residues. Ubiquitin is covalently bound to the purified PDGF receptor, the human gene for which is on chromosome 5.
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PMID:Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. 302 Apr 26

The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. Ubiquitin conjugation to protein is implicated in proteasome-dependent proteolytic pathway for short-lived proteins. In the present study, we have examined effects of different kinds of cell-penetrating proteasome inhibitors, including N-benzyloxycarbonyl-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-l eucinal (PSI) and a Streptomyces metabolite lactacystin, on ligand-stimulated degradation of the beta-receptor. These proteasome inhibitors were found to considerably inhibit the degradation of autophosphorylated and polyubiquitinated receptors, suggesting the possible involvement of proteasomes in the degradation process of the ligand-activated beta-receptor.
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PMID:Ligand-activated platelet-derived growth factor beta-receptor is degraded through proteasome-dependent proteolytic pathway. 852 15

Many cellular proteins are post-translationally modified by the addition of a single ubiquitin or a polyubiquitin chain. Among these are receptor tyrosine kinases (RTKs), which undergo ligand-dependent ubiquitination. The ubiquitination of RTKs has become recognized as an important signal for their endocytosis and degradation in the lysosome; however, it is not clear whether ubiquitination itself is sufficient for this process or simply participates in its regulation. The issue is further complicated by the fact that RTKs are thought to be polyubiquitinated - a modification that is linked to protein degradation by the proteasome. By contrast, monoubiquitination has been associated with diverse proteasome-independent cellular functions including intracellular protein movement. Here we show that the epidermal growth factor and platelet-derived growth factor receptors are not polyubiquitinated but rather are monoubiquitinated at multiple sites after their ligand-induced activation. By using different biochemical and molecular genetics approaches, we show that a single ubiquitin is sufficient for both receptor internalization and degradation. Thus, monoubiquitination is the principal signal responsible for the movement of RTKs from the plasma membrane to the lysosome.
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PMID:Multiple monoubiquitination of RTKs is sufficient for their endocytosis and degradation. 1271 48