EFFECT OF PHOSPHORYLATION ON INTERACTION OF P130CAS WITH AND-34

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 一个资助的项目（CA 114094 -01：人类乳腺癌中AND-34的分析）试图确定为什么特定蛋白质AND-34的过度表达会使正常雌激素依赖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。

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.