RESUMO
By the genetic selection of mouse cDNAs encoding secreted proteins, a B7-like cDNA clone termed mouse GL50 (mGL50) was isolated encoding a 322-aa polypeptide identical with B7h. Isolation of the human ortholog of this cDNA (hGL50) revealed a coding sequence of 309 aa residues with 42% sequence identity with mGL50. Northern analysis indicated GL50 to be present in many tissues including lymphoid, embryonic yolk sac, and fetal liver samples. Of the CD28, CTLA4, and ICOS fusion constructs tested, flow cytometric analysis demonstrated only mouse ICOS-IgG binding to mGL50 cell transfectants. Subsequent phenotyping demonstrated high levels of ICOS ligand staining on splenic CD19+ B cells and low levels on CD3+ T cells. These results indicate that GL50 is a specific ligand for the ICOS receptor and suggest that the GL50-ICOS interaction functions in lymphocyte costimulation.
Assuntos
Antígenos CD/isolamento & purificação , Antígenos de Diferenciação de Linfócitos T/metabolismo , Antígeno B7-1/isolamento & purificação , Glicoproteínas de Membrana/isolamento & purificação , Sequência de Aminoácidos , Animais , Antígenos CD/química , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno B7-1/química , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-2 , Northern Blotting , Clonagem Molecular , DNA Complementar/isolamento & purificação , Humanos , Ligante Coestimulador de Linfócitos T Induzíveis , Proteína Coestimuladora de Linfócitos T Induzíveis , Ligantes , Linfonodos/química , Linfonodos/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Proteínas/química , Alinhamento de Sequência , Transcrição Gênica/imunologia , Células Tumorais CultivadasRESUMO
Brain pathology in Alzheimer disease and in aged controls shows hyperphosphorylation of tau and of neurofilament proteins. Roder and Ingram [Roder, H.M. & Ingram, V.M. (1991) J. Neurosci. 11, 3325-3343 and Roder, H.M., Eden, P.A. & Ingram, V.M. (1993) Biochem. Biophys. Res. Commun. 193, 639-647] previously reported that the brain protein kinase PK40erk can hyperphosphorylate both tau and neurofilaments and interestingly, is strongly inhibited by ATP uncomplexed with Mg2+. We now report that the mitochondrial uncoupler carbonyl cyanide p-trifluoro-methoxyphenylhydrazone decreases ATP levels in rat pheochromacytoma (PC-12) cells differentiated with nerve growth factor and activates a neurofilament kinase, a tau kinase, and, unexpectedly, a tau phosphatase--either PP1 or PP2A. Such aberrant modulation of protein phosphorylation patterns could be the common biochemical basis for senile dementia and for Alzheimer disease and could explain the late-onset etiology of both conditions.