Casitas B-cell lymphoma (Cbl)-family E3 ubiquitin ligases are negative regulators of tyrosine kinase signaling. Recent work has revealed a critical role of Cbl in the maintenance of hematopoietic stem cell (HSC) homeostasis, and mutations in CBL have been identified in myeloid malignancies. Here we show that, in contrast to Cbl or Cbl-b single-deficient mice, concurrent loss of Cbl and Cbl-b in...

There is accumulating evidence for the existence of HNO in biological systems. Compared with NO (˙NO), much less is known about the chemical and biochemical reactivity of HNO. Kinetic and mechanistic studies have been carried out on the reaction between the vitamin B12-derived radical complex cob(II)alamin (Cbl(II)˙, Cbl(II)) with the widely used HNO donor Piloty's acid (PA). A stoichiometry of...

Phagocytosis mediated by FcgammaR plays an important role in host defense. The molecular events involved in this process have not been completely defined. The adapter protein Cbl has been implicated in FcgammaR signaling, but the function of Cbl in phagocytosis is unknown. Here we show that overexpression of the transforming mutants of Cbl, Cbl-70Z, and v-Cbl, but not wild-type (wt) Cbl, enhanc...

Methionine synthase catalyzes the conversion of N5-methyltetrahydrofolate and homocysteine to tetrahydrofolate and methionine. Methylcobalamin (Me-Cbl) is tightly bound to methionine synthase and is required for enzymatic activity. When added to crude tissue homogenates, Me-Cbl stimulates methionine synthase but similar stimulation is observed with hydroxocobalamin, cyanocobalamin (CN-Cbl), and...

The Cbl family of ubiquitin ligases in mammals contains three members, Cbl, Cbl-b, and Cbl-3, that are involved in down-regulation of receptor tyrosine kinases (RTKs) by mediating receptor ubiquitination and degradation. More recently, a novel pathway has been identified whereby Cbl promotes internalization of EGF receptor via a CIN85/endophilin pathway that is functionally separable from the u...

c-Cbl and Cbl-b E3 ubiquitin ligases are abundantly expressed in hemopoietic cells where they negatively regulate the activity and levels of many cell surface receptors and associated signaling molecules. By comparing bone marrow-derived mast cells from c-Cbl and Cbl-b-deficient mice it has recently been shown that Cbl-b is the dominant family member for negatively regulating signaling response...

The CBL ubiquitin ligase targets a variety of activated tyrosine kinases (TKs) for degradation. Many TKs are mutationally or autocrine activated and/or often overexpressed at the mRNA and protein levels in acute leukemias. We hypothesized that CBL is mutated in patients with acute myeloid leukemia (AML). Four of 12 patients and the MOLM-13 cell line harbored c-CBL mutations, either RNA splicing...

Recent reports indicate that oxidized cobalamin, Cbl(III), can interfere with the biological effects of nitric oxide (NO) on vascular and visceral smooth muscle and in other systems. In attempting to elucidate the mechanism of these effects of Cbl(III), we reported that a Cbl(III)NO complex could be detected by electron paramagnetic resonance (EPR) spectroscopy, but not by ultraviolet/visible s...

Paper reviews recent laboratory and numerical model studies of passive gaseous tracer dispersion in the atmospheric convective boundary layer (CBL) with surface and elevated wind shears. Atmospheric measurement data used for validation of these two model techniques are briefly discussed as well. A historical overview is given of laboratory studies of dispersion in the atmospheric CBL. Model stu...

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