Brdicková N, Brdicka T, Andera L, Spicka J, Angelisová P, Milgram S L, Horejsí V
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
FEBS Lett. 2001 Oct 26;507(2):133-6. doi: 10.1016/s0014-5793(01)02955-6.
Phosphoprotein associated with GEMs (PAG), also known as Csk-binding protein (Cbp), is a broadly expressed palmitoylated transmembrane adapter protein found in membrane rafts, also called GEMs (glycosphingolipid-enriched membrane microdomains). PAG is known to bind and activate the essential regulator of Src-family kinases, cytoplasmic protein tyrosine kinase Csk. In the present study we used the yeast 2-hybrid system to search for additional proteins which might bind to PAG. We have identified the abundant cytoplasmic adapter protein EBP50 (ezrin/radixin/moesin (ERM)-binding phosphoprotein of 50 kDa), also known as NHERF (Na(+)/H(+) exchanger regulatory factor), as a specific PAG-binding partner. The interaction involves the C-terminal sequence (TRL) of PAG and N-terminal PDZ domain(s) of EBP50. As EBP50 is known to interact via its C-terminal domain with the ERM-family proteins, which in turn bind to actin cytoskeleton, the PAG-EBP50 interaction may be important for connecting membrane rafts to the actin cytoskeleton.
与富含糖鞘脂膜微区(GEMs)相关的磷蛋白(PAG),也称为Csk结合蛋白(Cbp),是一种广泛表达的棕榈酰化跨膜衔接蛋白,存在于膜筏中,膜筏也称为GEMs(富含糖鞘脂的膜微区)。已知PAG可结合并激活Src家族激酶的重要调节因子——细胞质蛋白酪氨酸激酶Csk。在本研究中,我们使用酵母双杂交系统寻找可能与PAG结合的其他蛋白。我们鉴定出丰富的细胞质衔接蛋白EBP50(50 kDa的埃兹蛋白/根蛋白/膜突蛋白(ERM)结合磷蛋白),也称为钠氢交换调节因子(NHERF),作为PAG的特异性结合伴侣。这种相互作用涉及PAG的C末端序列(TRL)和EBP50的N末端PDZ结构域。由于已知EBP50通过其C末端结构域与ERM家族蛋白相互作用,而ERM家族蛋白又与肌动蛋白细胞骨架结合,因此PAG-EBP50相互作用可能对于将膜筏与肌动蛋白细胞骨架连接起来很重要。