994 resultados para Her-2 Neu Oncogene
Resumo:
Charles Hamilton Houston and other NAACP attorneys assembled in early October 1939 to take depositions in preparation for the hearing scheduled a week later in Columbia to determine whether the university had complied with the Gaines decision. Attorneys took depositions from all of the instructors of the new LU law school as their preparation for the court proceedings wound down. The deposition of Lloyd Gaines was next. Attorneys planned to ask Gaines whether he considered Lincoln to be as good of a law school as Missouri and whether he planned to enroll. Called for questioning, Gaines did not respond. He could not be located anywhere. Lloyd’s mother, Callie Gaines, recalled that in January her son “left here to go to Kansas City to make a speech. That’s the last I saw of him.” While in Kansas City, Gaines spoke at the Centennial Methodist Church. He also looked for work, but not finding any caught a train for Chicago, telling people in Kansas City that he would stay a few days and return home.
Resumo:
Multiple human skeletal and craniosynostosis disorders, including Crouzon, Pfeiffer, Jackson–Weiss, and Apert syndromes, result from numerous point mutations in the extracellular region of fibroblast growth factor receptor 2 (FGFR2). Many of these mutations create a free cysteine residue that potentially leads to abnormal disulfide bond formation and receptor activation; however, for noncysteine mutations, the mechanism of receptor activation remains unclear. We examined the effect of two of these mutations, W290G and T341P, on receptor dimerization and activation. These mutations resulted in cellular transformation when expressed as FGFR2/Neu chimeric receptors. Additionally, in full-length FGFR2, the mutations induced receptor dimerization and elevated levels of tyrosine kinase activity. Interestingly, transformation by the chimeric receptors, dimerization, and enhanced kinase activity were all abolished if either the W290G or the T341P mutation was expressed in conjunction with mutations that eliminate the disulfide bond in the third immunoglobulin-like domain (Ig-3). These results demonstrate a requirement for the Ig-3 cysteine residues in the activation of FGFR2 by noncysteine mutations. Molecular modeling also reveals that noncysteine mutations may activate FGFR2 by altering the conformation of the Ig-3 domain near the disulfide bond, preventing the formation of an intramolecular bond. This allows the unbonded cysteine residues to participate in intermolecular disulfide bonding, resulting in constitutive activation of the receptor.