EFFECT OF PHOSPHORYLATION ON INTERACTION OF P130CAS WITH AND-34

磷酸化对 P130CAS 与 AND-34 相互作用的影响

• 批准号: 7723076
• 负责人: ADAM LERNER
• 金额: $ 0.2万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723076
• 关键词: Adherence; Affect; B-Lymphocytes; Binding; Breast Cancer Cell; Cancer cell line; Cell Line; Computer Retrieval of Information on Scientific Projects Database; Cyclin D1; Estrogen Antagonists; Estrogens; Family member; Focal Adhesions; Funding; Grant; Growth; Human; Institution; Lymphoid; MCF7 cell; Mass Spectrum Analysis; Mus; Pattern; Phosphorylation; Play; Proteins; Research; Research Personnel; Resistance; Resources; Role; Source; United States National Institutes of Health; adapter protein; human BCAR1 protein; malignant breast neoplasm; migration; promoter; src-Family Kinases

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A funded project (CA114094-01: Analysis of AND-34 in human breast cancer) seeks to establish why over-expression of a specific protein, AND-34, allows normally estrogen-dependent human breast cancer cell lines to become resistant to growth inhibition by anti-estrogens. AND-34 is expressed in murine B cells and plays a role in lymphoid adherence and migration. We have shown that AND-34 binds to a focal adhesion adapter protein, p130Cas. Over-expression of AND-34, but not two other closely related family members (NSP-1 and NSP-2) leads to activation of the cyclin D1 promoter and anti-estrogen resistance. All three family members bind to p130Cas. There is some evidence that over-expression of AND-34 may affect phosphorylation of p130Cas. This does not appear to occur by a Src family kinase-dependent mechanism, although p130Cas is a well known Src family kinase substrate. We are using mass spectrometry to establish where p130Cas is phosphorylated following over-expression of AND-34. We will compare the phosphorylation pattern of p130Cas from this AND-34 over-expressing cell line with that observed in MCF-7 cells.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 一个受资助的项目（CA 114094 -01：人类乳腺癌中AND-34的分析）旨在确定为什么特定蛋白质AND-34的过度表达会使通常雌激素依赖性的人类乳腺癌细胞系对抗雌激素的生长抑制产生抗性。AND-34在鼠B细胞中表达，并在淋巴粘附和迁移中起作用。我们已经表明，AND-34结合到一个粘着斑适配蛋白，p130 Cas。AND-34的过表达，而不是其他两个密切相关的家族成员（NSP-1和NSP-2）导致细胞周期蛋白D1启动子的激活和抗雌激素抗性。所有三个家族成员都与p130 Cas结合。 有证据表明AND-34的过表达可能影响p130 Cas的磷酸化。虽然p130 Cas是一种众所周知的Src家族激酶底物，但这似乎不是通过Src家族激酶依赖性机制发生的。我们正在使用质谱法来确定AND-34过表达后p130 Cas磷酸化的位置。我们将比较从该AND-34过表达细胞系与在MCF-7细胞中观察到的p130 Cas的磷酸化模式。