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Rac1 / Cdc42 - 版本历史
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<strong>Rac1</strong>（Ras-related C3 botulinum toxin substrate 1）是 Rho GTP 酶家族的核心成员，在调控细胞骨架重排、细胞迁移和极性形成中起决定性作用。其标志性的生物学功能是诱导细胞边缘产生扇形的<strong>[[层状伪足]]</strong>（Lamellipodia）。Rac1 通过在活化的 GTP 结合态与失活的 GDP 结合态之间切换，像“分子开关”一样控制信号。在临床上，Rac1 的异常激活广泛参与了恶性肿瘤的<strong>[[上皮-间质转化]]</strong>（EMT）、药物耐药以及心血管重塑过程。<br />
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<div style="font-size: 1.1em; font-weight: bold; letter-spacing: 1.2px;">[[Rac1]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">Rho家族成员 / 分子开关 · 点击展开</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心效应：层状伪足形成</div><br />
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<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">Entrez ID</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5879</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">HGNC ID</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">9801</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">UniProt ID</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">P63000</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">21 kDa</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">染色体</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">7p22.1</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">药理靶点</th><td style="padding: 12px; color: #b91c1c;">PAK1, WAVE</td></tr><br />
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<li style="margin-bottom: 12px;"><strong>WAVE 复合体激活：</strong> 活化的 Rac1-GTP 结合并招募 <strong>[[WAVE]]</strong> 复合体，进而激活 <strong>[[Arp2/3]]</strong> 蛋白，诱导肌动蛋白发生分叉聚合，推动细胞膜前缘形成层状伪足。</li><br />
<li style="margin-bottom: 12px;"><strong>氧化应激调节：</strong> Rac1 是 <strong>[[NADPH 氧化酶]]</strong>（NOX）复合物的关键组分，调控活性氧（ROS）的产生，参与细胞信号扩增及血管平滑肌增生。</li><br />
<li style="margin-bottom: 12px;"><strong>PAK 信号通路：</strong> 通过磷酸化 <strong>[[PAK1]]</strong>（p21 活化激酶），Rac1 调节微管稳定性和基因转录。</li><br />
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<strong>Cdc42</strong>（Cell division control protein 42 homolog）是 Rho 家族中负责调控“细胞导航”和极性的关键分子。其最显著的功能是诱导产生指状的<strong>[[丝状伪足]]</strong>（Filopodia），用于感知外部环境微环境变化。Cdc42 不仅在细胞迁移中指引方向，还广泛参与内吞、胞吐及轴突发育。Cdc42 的功能障碍常导致严重的<strong>[[发育畸形]]</strong>或免疫缺陷。<br />
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<div style="font-size: 1.1em; font-weight: bold; letter-spacing: 1.2px;">[[Cdc42]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">细胞极性调节器 · 点击展开</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心效应：丝状伪足/极化</div><br />
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<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">Entrez ID</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">998</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">HGNC ID</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1736</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">UniProt ID</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">P60953</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">21 kDa</td></tr><br />
<tr><th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">下游底物</th><td style="padding: 12px; color: #b91c1c;">WASP, N-WASP, Par-6</td></tr><br />
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<li style="margin-bottom: 12px;"><strong>WASP 活化机制：</strong> Cdc42-GTP 通过结合 <strong>[[WASP]]</strong> 或 N-WASP，解除其自抑制状态，激活 Arp2/3 复合体产生丝状伪足。</li><br />
<li style="margin-bottom: 12px;"><strong>极性复合物构建：</strong> Cdc42 与 <strong>[[Par6/Par3/aPKC]]</strong> 蛋白组装，在神经元轴突定向、上皮细胞顶端-基底极化中起核心作用。</li><br />
<li style="margin-bottom: 12px;"><strong>胞内运输：</strong> 参与高尔基体与细胞膜之间的微管依赖性物质转运。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">临床对比：Rac1 vs Cdc42</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1;">对比维度</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1;">Rac1</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1;">Cdc42</th><br />
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<tr><td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: bold;">主要突起</td><td style="padding: 8px; border: 1px solid #cbd5e1;">层状伪足 (宽扇形)</td><td style="padding: 8px; border: 1px solid #cbd5e1;">丝状伪足 (细指状)</td></tr><br />
<tr><td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: bold;">临床相关疾病</td><td style="padding: 8px; border: 1px solid #cbd5e1;">肿瘤侵袭、糖尿病肾病</td><td style="padding: 8px; border: 1px solid #cbd5e1;">Takenouchi-Kosaki 综合征</td></tr><br />
<tr><td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: bold;">生化标志</td><td style="padding: 8px; border: 1px solid #cbd5e1;">p-PAK1 升高</td><td style="padding: 8px; border: 1px solid #cbd5e1;">Par 复合物定位异常</td></tr><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[RhoA]]</strong>：Rho 家族的另一支柱，主要负责应力纤维形成。</li><br />
<li style="margin-bottom: 8px;"><strong>[[GEFs/GAPs]]</strong>：调控 Rac1/Cdc42 GTP 循环的上游分子。</li><br />
<li style="margin-bottom: 12px;"><strong>[[WASP 蛋白]]</strong>：Cdc42 的直接下游，负责连接极性信号与骨架聚合。</li><br />
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<span style="color: #0f172a; font-weight: bold;">学术参考文献 [Academic Review]</span><br />
<p style="margin: 12px 0;">[1] <strong>Hall A. (1998).</strong> <em>Rho GTPases and the actin cytoskeleton.</em> <strong>[[Science]]</strong>.<br>[2] <strong>Nobes CD, Hall A. (1995).</strong> <em>Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes.</em> <strong>[[Cell]]</strong>.</p><br />
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