RESUMO
Efficient directed migration requires tight regulation of chemoattractant signal transduction pathways in both space and time, but the mechanisms involved in such regulation are not well understood. Here, we investigated the role of protein kinase A (PKA) in controlling signaling of the chemoattractant cAMP in Dictyostelium discoideum We found that cells lacking PKA display severe chemotaxis defects, including impaired directional sensing. Although PKA is an important regulator of developmental gene expression, including the cAMP receptor cAR1, our studies using exogenously expressed cAR1 in cells lacking PKA, cells lacking adenylyl cyclase A (ACA) and cells treated with the PKA-selective pharmacological inhibitor H89, suggest that PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1 and TORC2. As these pathways control the ACA-mediated production of intracellular cAMP, they lie upstream of PKA in this chemoattractant signaling network. Consequently, we propose that the PKA-mediated regulation of the upstream RasG, Rap1 and TORC2 signaling pathways is part of a negative feedback mechanism controlling chemoattractant signal transduction during Dictyostelium chemotaxis.
Assuntos
Fatores Quimiotáticos/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dictyostelium/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteínas de Protozoários/metabolismo , Transdução de Sinais , Proteínas rap1 de Ligação ao GTP/metabolismo , Proteínas ras/metabolismo , Actinas/metabolismo , Quimiotaxia , Dictyostelium/citologia , Dictyostelium/efeitos dos fármacos , Modelos Biológicos , Miosinas/metabolismo , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
AIMS: The aim of this study is to assess the awareness about cervical cancer and the acceptability of cytological screening and vaccine against human papilloma virus (HPV) among women in Delhi, the national capital of India. MATERIALS AND METHODS: A cross-sectional survey of women was conducted in Delhi to assess the awareness of cervical cancer and acceptability of Papanicolaou (Pap) test and HPV vaccine. The sample size of the population was 450, and a pre-tested questionnaire was administered to them. RESULTS: Majority of the participants (85.11%) were aware of cervical cancer and were willing to undergo diagnosis by Pap test (84.6%). As far as vaccination was concerned, 63.14% found the HPV vaccine acceptable for their daughters. However, very few participants were willing to vaccinate themselves against HPV. CONCLUSION: The high awareness among females in Delhi about cervical cancer and acceptability of screening programs, if done free of cost, shows a positive trend. The only inhibition about HPV vaccine was primarily due to concerns about postvaccination complications. However, inclusion of HPV vaccine in Government-sponsored immunization program would go a long way in increasing the acceptability of the vaccine.