Vitamin B(12), viz., cyano- or hydroxo-cobalamin, can be chemically or enzymatically converted into the derivatives methyl- and adenosyl-cobalamin, which are complex organometallic cofactors associated with several cobalamin-dependent enzymes. The reduced form of vitamin B(12), cob(I)alamin {Cbl(I)}, obtained by reduction of hydroxocobalamin (OH-Cbl) with e.g. sodium borohydride, is one of the ...

The induction of protein tyrosine kinase signaling pathways is a principal mechanism for promoting cellular activation. Biochemical and genetic analyses have implicated the multi-adaptor proto-oncogene protein Cbl as a key negative regulator of activated protein tyrosine kinases. By inhibiting the function of Cbl as a multi-domain adaptor protein, through expression of a truncated form (480-Cbl...

We analyzed 636 patients with diverse myeloproliferative neoplasms or myelodysplastic/myeloproliferative neoplasms for mutations of the Casitas B-cell lymphoma gene (CBL(mut)) in exons 8 and 9 and performed correlations to other genetic alterations. CBL(mut) were detected in 63 of 636 (9.9%) of these selected patients. CBL(mut) were more frequent in myelodysplastic/myeloproliferative neoplasms ...

BACKGROUND Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activa...

The 120-kDa protein product of the c-Cbl proto-oncogene is a ubiquitously expressed cytoplasmic protein that is especially abundant in the thymus, indicating an important role for Cbl in thymic signalling. c-Cbl possesses a highly conserved N-terminal phosphotyrosine binding domain, a C3HC4 RING finger motif, multiple proline-rich motifs, and a number of potential tyrosine phosphorylation sites...

BACKGROUND Non-small cell lung carcinoma (NSCLC) mainly includes lung squamous cell carcinoma and adenocarcinoma. This study aimed to investigate the difference between the expression of Cbl-b in lung squamous cell carcinoma and adenocarcinoma. MATERIAL AND METHODS The clinical features and survival data of NSCLC patients and Cbl-b mRNA (FPKM) were obtained from the TCGA database. Then, lung sq...

Queuosine (Q) was discovered in the wobble position of a transfer RNA (tRNA) 47 years ago, yet the final biosynthetic enzyme responsible for Q-maturation, epoxyqueuosine (oQ) reductase (QueG), was only recently identified. QueG is a cobalamin (Cbl)-dependent, [4Fe-4S] cluster-containing protein that produces the hypermodified nucleoside Q in situ on four tRNAs. To understand how QueG is able to...

To identify novel signal transducers involved in signaling mediated by the Src-family protein tyrosine kinases (PTKs), we used a yeast two-hybrid system with a probe corresponding to the regulatory region of p56lyn, a member of Src-family PTKs. One of the isolated clones contained the COOH-terminal 470 amino acid residues of p120c-cbl, the product of the cellular homologue of the v-cbl retrovir...

The proto-oncogene product, Cbl, is a 120-kDa protein present in lymphocytes that contains numerous PXXP motifs in its COOH-terminal region and constitutively binds the SH3-containing adaptor protein Grb2. Cross-linking of CD3 and CD4 receptors in Jurkat T cells causes tyrosine phosphorylation of Cbl and its association with phosphatidylinositol 3'-kinase (Meisner, H., Conway, B., Hartley, D., ...

Transcobalamin (TC) -encoding cDNA was isolated from a bovine mammary gland cDNA library. Hybridization of the cloned bovine TC-cDNA to RNA samples from bovine tissues showed that the most intensive synthesis of a TC positive 1.9-kilobase mRNA occurred in kidney, lymphatic nodes, and liver. Bovine TC was expressed in yeast Pichia pastoris, and the isolated recombinant protein showed cobalamin (...