RHO GTPases 调节 CFTR 转运
中文名称
通路描述
活化的 RHO GTPase RHOQ (TC10) 通过结合 GOPC (Golgi-associated and PDZ and coiled-coil motif-containing protein) 也称为 PIST、FIG 或 CAL 来调节 CFTR (cystic fibrosis transmembrane conductance regulator) 的转运。GOPC 是 Golgi 驻留蛋白，可结合多种膜蛋白，从而调节其表达。在没有 RHOQ 的情况下，GOPC 结合 CFTR 将 CFTR 导向溶酶体降解，而 GTP 结合的 RHOQ 则将 GOPC:CFTR 复合物导向质膜，从而挽救 CFTR (Neudauer et al. 2001, Cheng et al. 2005)。
英文描述
RHO GTPases Activate WASPs and WAVEs WASP and WAVE proteins belong to the Wiskott-Aldrich Syndrome protein family, with recessive mutations in the founding member WASP being responsible for the X-linked recessive immunodeficieny known as the Wiskott-Aldrich Syndrome. WASP proteins include WASP and WASL (N-WASP). WAVE proteins include WASF1 (WAVE1), WASF2 (WAVE2) and WASF3 (WAVE3). WASPs and WAVEs contain a VCA domain (consisting of WH2 and CA subdomains) at the C-terminus, responsible for binding to G-actin (WH2 subdomain) and the actin-associated ARP2/3 complex (CA subdomain). WASPs contain a WH1 (WASP homology 1) domain at the N-terminus, responsible for binding to WIPs (WASP-interacting proteins). A RHO GTPase binding domain (GBD) is located in the N-terminal half of WASPs and C-terminally located in WAVEs. RHO GTPases activate WASPs by disrupting the autoinhibitory interaction between the GBD and VCA domains, which allows WASPs to bind actin and the ARP2/3 complex and act as nucleation promoting factors in actin polymerization. WAVEs have the WAVE/SCAR homology domain (WHD/SHD) at the N-terminus, which binds ABI, NCKAP1, CYFIP2 and BRK1 to form the WAVE regulatory complex (WRC). Binding of the RAC1:GTP to the GBD of WAVEs most likely induces a conformational change in the WRC that allows activating phosphorylation of WAVEs by ABL1, thus enabling them to function as nucleation promoting factors in actin polymerization through binding G-actin and the ARP2/3 complex (Reviewed by Lane et al. 2014).
所含基因
36 个基因