Cbls

Because of their many interactions, Cbls were logically thought of as scaffolds for signaling and endocytosis. It is now apparent that Cbls target many tyrosine 

The first clue to a relationship between Cbl and ubiquitylation came from Stanley and co-workers who demonstrated that c-Cbl was mono-ubiquitylated in response to CSE-1 (colony stimulating fiictor-1) [193]. Yarden and colleagues demonstrated an association between Cbl recruitment to receptors and their ubiquitylation and down-regulation. C-Cbl E3 ligase activity was subsequently demonstrated by several groups [31, 184, 186). 

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The methylene grou]) (CbL) standing between two CO groups, such as occurs in acetoacctic ester, is characterised by cerltiin pro]icrties, which are shared hy all compounds of similar strurUire, vi/., by their behaviour towards nitrous acid, diazo-ben/.ene s.alts, and met.allic sodium or sodium alcohokate. 

Inspection Personnel, Abington Hall, Abington, Cambridge CBl 6AL SCI Society of Chemical Industry, 14-15... 

Fujita Y, Krause G, Scheffner M et al (2002) Hakai, a c-Cbl-like protein, ubiquitinates and induces endo-cytosis of the E-cadherin complex. Nat Cell Biol 4(3) 222-231... 

Among the substrates of Src are other nonreceptor PTKs (e.g., Fak, Syk, and Tec kinases), RTKs (e.g. EGF and PDGF receptors), phospholipase Cy, PI3-kinase, phosphatases (e.g., SHP-2 and PP2A), and adaptor (e.g., She and Cbl) as well as focal adhesion proteins (e.g., paxillin, pl30Cas andtensin). Src-mediated phosphorylation either modulates enzymatic activity of... 

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Research on CBl knockout mice demonstrated the pivotal role of CBl receptors in cannabis dependence knockout mice have been shown not to self-administer cannabinoids (Ledent et al. 1999) and also to fail to exhibit symptoms ofSRl417l6A-precipitated withdrawal (Ledent et al. 1999 Lichtman et al. 2001). Although the research summarized earlier is consistent in reporting the occurrence of a variety of withdrawal symptoms following cessation of exposure to cannabinoids (which were injected), precipitated withdrawal in mice following chronic exposure to marijuana smoke was more recently reported (Lichtman and Martin 2002). 

Compton WM, Grant BF, Colliver JD, et al Prevalence of marijuana use disorders in the United States 1991-1992 and2001-2002. JAMA291 2114-2121,2004 Cook SA, Lowe JA, Martin BR CBl receptor antagonist precipitates withdrawal in mice exposed to delta9-tetrahydrocannabinol. J Pharmacol Exp Ther 285 1150— 1156, 1998... 

Fattore L, Cossu G, Martellotta CM, et al Intravenous self-administration of the Cbl receptor agonist WIN 55,212—2 in rats. Psychopharmacology (Berl) 156 410-416, 2001... 

Fride E, Foox A, Rosenberg E, et al Milk intake and survival in newborn cannabinoid CBl receptor knockout mice evidence for a CB3 receptor. EurJ Pharmacol 461 27-34, 2003... 

Ledent C, Valverde L, Cossu G, et al Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CBl receptor knockout mice. Science 283 401-404, 1999... 

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