Glial cell line-derived neurotrophic factor (GDNF) plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are medi...Glial cell line-derived neurotrophic factor (GDNF) plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha1 (GFRα1), and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFRα1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFRα1 mutations was made, and PC12 cell lines stably expressing different GFRα1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF-GFRα1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFRα1 central region were found to be critical for GFRα1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFRα1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/S318A mutation in the GFRα1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFRα1 may be involved in binding to GDNF and Ret.展开更多
Background and Objective Lung cancer is the most lethal malignangy that threatens human health and lives nowadays in the world, The overall cure rate of lung cancer is only 13% -15%,
Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the
Background and Objective Lung cancer is one of the most malignant cancers which is hazarding the people’s health and life in the world. In the past half century, the incidence and mortality
Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by
Background and Objective Lung cancer, which threatens human’s health and life, is the malignant tumor with the most rapid increase of morbidity. Although recent years the basic
Background and Objective Lung cancer is the rst killer of human being in the whole world. Recently, although many treatment strategies have been developed, the anti-cancer effects
Background and objective Lung Cancer is one of the most malignant cancers threatening people’s health and life and one of the most rapid increasing cancers both in morbidity
Backgroud and Objective At present, lung cancer has become the most frenquent malignant tumor in China and in the world which its mortality and morbidity is increasing fastest.
Background and Objective Lung cancer is not only the most dangerous threating tumor to human’s health and life, but also a malignant tumor with poor prognosis. In the past 10 years,
Background and Objective Lung cancer is not only the most dangerous threating tumor to humans health and life, but also a malignant tumor with poor prognosis. It has been
Background and Objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. To study and elucidate the molecular mechanism
文摘Glial cell line-derived neurotrophic factor (GDNF) plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha1 (GFRα1), and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFRα1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFRα1 mutations was made, and PC12 cell lines stably expressing different GFRα1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF-GFRα1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFRα1 central region were found to be critical for GFRα1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFRα1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/S318A mutation in the GFRα1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFRα1 may be involved in binding to GDNF and Ret.
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Lung cancer is the most lethal malignangy that threatens human health and lives nowadays in the world, The overall cure rate of lung cancer is only 13% -15%,
基金supported by grants from National Natural Sciences Foundation of China (to Qinghua ZHOU, No.3007033 )
文摘Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Lung cancer is one of the most malignant cancers which is hazarding the people’s health and life in the world. In the past half century, the incidence and mortality
基金supported by the grants from the Key Project of National Natural Science Foundation of China (No .30430300 , to Qinghua ZHOU)Key Projects of Tian-jin Sci-Tech Support Program (No . 07SY SY SF05000 and No 06YFSZSF05300, to Qinghua ZHOU)
文摘Objective and Methods The key cause of failure to cure and high mortality in lung cancer. At present, it has been known
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30670922)
文摘Background and Objective Lung cancer, which threatens human’s health and life, is the malignant tumor with the most rapid increase of morbidity. Although recent years the basic
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Lung cancer is the rst killer of human being in the whole world. Recently, although many treatment strategies have been developed, the anti-cancer effects
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU) (No. 30430300)
文摘Background and objective Lung Cancer is one of the most malignant cancers threatening people’s health and life and one of the most rapid increasing cancers both in morbidity
基金supported by the Key Project of National Natural Sciences Fundation of China (to Qinghua ZHOU) (No. 30430300)grant from the National Natural Science Foundation of China. ( to Qinghua ZHOU)(No.3007033 )
文摘Backgroud and Objective At present, lung cancer has become the most frenquent malignant tumor in China and in the world which its mortality and morbidity is increasing fastest.
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Lung cancer is not only the most dangerous threating tumor to human’s health and life, but also a malignant tumor with poor prognosis. In the past 10 years,
文摘Background and Objective Lung cancer is not only the most dangerous threating tumor to humans health and life, but also a malignant tumor with poor prognosis. It has been
基金supported by a grant from the key project of the National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30430300)National Natural Science Foundation of China (to Qinghua ZHOU)(No. 30670922)INTERNATION Scienc and Techniquie COOPRATION PROGRAM OF CHINA (ISCP) (to Qinghua ZHOU)(No.2006DFB32330)
文摘Background and Objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. To study and elucidate the molecular mechanism
