Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azatyrosine [L-beta-(5-hydroxy-2-pyridyl)-alanine] has the unique property of converting ras- or c-erbB-2 transformed phenotype to normal. The administration of azatyrosine also inhibits tumor formation in transgenic mice harboring the normal human c-Ha-ras which is mutated during treatment with various chemical carcinogens. To elucidate the molecular mechanism, we investigated how azatyrosine functions and what are its major targets. Azatyrosine functions downstream of ras; azatyrosine does not alter either the level of GTP-bound Ras or the total amount of Ras. Instead, azatyrosine inhibits the activation of c-Raf-1 kinase by oncogenic c-ErbB-2, resulting in inactivation of AP1. It is interesting that azatyrosine also restores the expression of the rhoB gene, the product of which regulates the formation of actin stress fibers. Azatyrosine is incorporated into cellular proteins to replace tyrosine. Several experiments indicate that replacement of tyrosine is likely to be a cause for its conversion of transformed phenotype to normal. To prove this hypothesis, we are attempting to develop a mutant of tyrosyl-tRNA synthetase that, unlike wild type, can aminoacylate azatyrosine more efficiently than can tyrosine.
 ...
PMID:Azatyrosine. Mechanism of action for conversion of transformed phenotype to normal. 1066 9

We report a method of photo-cross-linking proteins in mammalian cells, which is based on site-specific incorporation of a photoreactive amino acid, p-benzoyl-L-phenylalanine (pBpa), through the use of an expanded genetic code. To analyze the cell signaling interactions involving the adaptor protein Grb2, pBpa was incorporated in its Src homology 2 (SH2) domain. The human GRB2 gene with an amber codon was introduced into Chinese hamster ovary (CHO) cells, together with the genes for the Bacillus stearothermophilus suppressor tRNA(Tyr) and a pBpa-specific variant of Escherichia coli tyrosyl-tRNA synthetase (TyrRS). The Grb2 variant with pBpa in the amber position was synthesized when pBpa was included in the growth medium. Upon exposure of cells to 365-nm light, protein variants containing pBpa in the positions proximal to the ligand-binding pocket were cross-linked with the transiently expressed epidermal growth factor (EGF) receptor in the presence of an EGF stimulus. Cross-linked complexes with endogenous proteins were also detected. In vivo photo-cross-linking with pBpa incorporated in proteins will be useful for studying protein-protein interactions in mammalian cells.
 ...
PMID:Protein photo-cross-linking in mammalian cells by site-specific incorporation of a photoreactive amino acid. 1578 89