RHO GTPases 激活 WASPs 和 WAVEs
中文名称
通路描述
WASP 和 WAVE 蛋白属于 Wiskott-Aldrich 综合征蛋白家族，WASP 基因（特别是 WASP 和 WASL）的隐性突变导致 X 连锁隐性免疫缺陷病 Wiskott-Aldrich 综合征。WAVE 蛋白包括 WASF1（WAVE1）、WASF2（WAVE2）和 WASF3（WAVE3）。WASP 和 WAVE 在 C 端含有 VCA 结构域（由 WH2 和 CA 结构域组成），负责与 G-actin（WH2 结构域）和 actin 相关蛋白复合物 ARP2/3（CA 结构域）结合。WASP 在 N 端含有 WH1 结构域，负责与 WIPs（WASP 相互作用蛋白）结合。RHO GTPase 结合结构域（GBD）位于 WASP 的 N 端一半和 WAVE 的 C 端。RHO GTPase 通过破坏 GBD 与 VCA 结构域之间的自抑制相互作用来激活 WASP，使 WASP 能够结合 actin 和 ARP2/3 复合物，作为 actin 聚合的核促进因子。WAVE 在 N 端含有 WAVE/SCAR 同源结构域（WHD/SHD），可结合 ABI、NCKAP1、CYFIP2 和 BRK1 形成 WAVE 调节复合物（WRC）。RAC1:GTP 结合 WAVE 的 GBD 最可能诱导 WRC 构象变化，允许 ABL1 磷酸化 WAVE，从而使其通过结合 G-actin 和 ARP2/3 复合物作为 actin 聚合的核促进因子发挥作用（参考 Lane et al. 2014）。
英文描述
Pre-NOTCH Processing in the Endoplasmic Reticulum In the endoplasmic reticulum, glycosyl transferases modify NOTCH precursors by glycosylating conserved serine and threonine residues in EGF repeats of NOTCH.
O-fucosyl transferase POFUT1 fucosylates NOTCH serine and threonine residues that conform to the consensus sequence C2-X(4-5)-S/T-C3, where C2 and C3 are the second and third cysteine residue within the EGF repeat, and X(4-5) is four to five amino acid residues of any type (Yao et al. 2011, Stahl et al. 2008, Wang et al. 2001, Shao et al. 2003).
O-glucosyl transferase POGLUT1, mammalian homolog of the Drosophila enzyme Rumi, adds a glucosyl group to conserved serine residues within the EGF repeats of NOTCH. The consensus sequence for POGLUT1-mediated glucosylation is C1-X-S-X-P-C2, where C1 and C2 are the first and second cysteine residue in the EGF repeat, respectively, while X represents any amino acid (Acar et al. 2008, Fernandez-Valdivia et al. 2011). Both fucosylation and glucosylation of NOTCH receptor precursors are essential for functionality.
O-fucosyl transferase POFUT1 fucosylates NOTCH serine and threonine residues that conform to the consensus sequence C2-X(4-5)-S/T-C3, where C2 and C3 are the second and third cysteine residue within the EGF repeat, and X(4-5) is four to five amino acid residues of any type (Yao et al. 2011, Stahl et al. 2008, Wang et al. 2001, Shao et al. 2003).
O-glucosyl transferase POGLUT1, mammalian homolog of the Drosophila enzyme Rumi, adds a glucosyl group to conserved serine residues within the EGF repeats of NOTCH. The consensus sequence for POGLUT1-mediated glucosylation is C1-X-S-X-P-C2, where C1 and C2 are the first and second cysteine residue in the EGF repeat, respectively, while X represents any amino acid (Acar et al. 2008, Fernandez-Valdivia et al. 2011). Both fucosylation and glucosylation of NOTCH receptor precursors are essential for functionality.
所含基因
6 个基因