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JAK-STAT3 信号通路 - 版本历史
2026-04-18T21:42:58Z
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2025年12月29日 (一) 03:09 223.160.136.32
2025-12-29T03:09:47Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2025年12月29日 (一) 03:09的版本</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <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; text-decoration: none;">分子传导：从 gp130 到核易位</h2><del class="diffchange diffchange-inline"><p style="margin: 15px 0; text-align: justify;"></del></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <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; text-decoration: none;">分子传导：从 gp130 到核易位</h2></p></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> JAK-STAT3 通路的激活是一场高度程序化的分子接力，其核心步骤如下：</del></div></td><td colspan="2"> </td></tr>
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223.160.136.32
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2025年12月29日 (一) 03:09 223.160.136.32
2025-12-29T03:09:13Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2025年12月29日 (一) 03:09的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l17" >第17行：</td>
<td colspan="2" class="diff-lineno">第17行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="padding: 35px; text-align: center; background-color: #f8fafc;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <div style="padding: 35px; text-align: center; background-color: #f8fafc;"></div></td></tr>
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<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> [[文件:JAK_STAT3_Molecular_Icon.png|110px|STAT3 磷酸化与入核示意图]]</div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> [[文件:JAK_STAT3_Molecular_Icon.png|110px|STAT3 磷酸化与入核示意图<ins class="diffchange diffchange-inline">|链接=Special:FilePath/JAK_STAT3_Molecular_Icon.png</ins>]]</div></td></tr>
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<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l44" >第44行：</td>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </div></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <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; text-decoration: none;">分子传导：从 gp130 到核易位</h2></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <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; text-decoration: none;">分子传导：从 gp130 到核易位</h2><p style="margin: 15px 0; text-align: justify;"></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> [Image showing the IL-6/gp130/JAK/STAT3 signaling cascade]</del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> </del><p style="margin: 15px 0; text-align: justify;"></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> JAK-STAT3 通路的激活是一场高度程序化的分子接力，其核心步骤如下：</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> JAK-STAT3 通路的激活是一场高度程序化的分子接力，其核心步骤如下：</div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </p></div></td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del class="diffchange diffchange-inline"> </del></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> </div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </ins></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> [1] <strong>Darnell JE, et al. (1994).</strong> <em>Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.</em> <strong>Science</strong>. <br></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> [1] <strong>Darnell JE, et al. (1994).</strong> <em>Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.</em> <strong>Science</strong>. <br></div></td></tr>
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223.160.136.32
https://www.yiliao.com/index.php?title=JAK-STAT3_%E4%BF%A1%E5%8F%B7%E9%80%9A%E8%B7%AF&diff=311332&oldid=prev
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2025-12-29T03:06:10Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>JAK-STAT3 信号通路</strong>（JAK-STAT3 Signaling Pathway）是 <strong>[[JAK-STAT 通路]]</strong> 中研究最广泛、临床意义最显著的分支。该通路主要响应 <strong>[[IL-6]] 家族</strong>、IL-10 家族细胞因子的刺激，通过激活 <strong>[[STAT3]]</strong> 转录因子，直接调控细胞增殖、存活、血管生成及免疫抑制。在[[临床肿瘤学]]中，JAK-STAT3 的持续激活是恶性肿瘤逃避凋亡、建立免疫抑制微环境（TME）以及引发严重 <strong>[[CRS]]</strong>（细胞因子释放综合征）的关键分子机理。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px; text-decoration: none !important;">JAK-STAT3 · 核心转录调控</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">JAK-STAT3 Axis Profile (点击展开)</div><br />
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[[文件:JAK_STAT3_Molecular_Icon.png|110px|STAT3 磷酸化与入核示意图]]<br />
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<div style="font-size: 0.85em; color: #64748b; margin-top: 15px; font-weight: 600;">IL-6 驱动的核易位模型</div><br />
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<th style="text-align: left; padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc; width: 40%;">核心激酶</th><br />
<td style="padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">JAK1, JAK2, TYK2</td><br />
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<th style="text-align: left; padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">主控因子</th><br />
<td style="padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">STAT3 (Tyr705 磷酸化)</td><br />
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<th style="text-align: left; padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #475569; background-color: #f8fafc;">下游靶基因</th><br />
<td style="padding: 10px 15px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">Bcl-2, Myc, VEGF, CRP</td><br />
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<th style="text-align: left; padding: 10px 15px; color: #475569; background-color: #f8fafc;">拮抗手段</th><br />
<td style="padding: 10px 15px; color: #1e40af; font-weight: 600;">[[托珠单抗]], 鲁索替尼</td><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; text-decoration: none;">分子传导：从 gp130 到核易位</h2><br />
[Image showing the IL-6/gp130/JAK/STAT3 signaling cascade]<br />
<p style="margin: 15px 0; text-align: justify;"><br />
JAK-STAT3 通路的激活是一场高度程序化的分子接力，其核心步骤如下：<br />
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<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>配体识别与受体组装：</strong> IL-6 与其受体 IL-6R 结合后，募集跨膜信号转导蛋白 <strong>[[gp130]]</strong> 形成六聚体复合物。</li><br />
<li style="margin-bottom: 12px;"><strong>JAK 交叉磷酸化：</strong> 结合在 gp130 胞内端的 <strong>JAK1/2</strong> 相互靠近并激活，随后磷酸化受体尾部的酪氨酸位点，为 STAT3 提供结合平台。</li><br />
<li style="margin-bottom: 12px;"><strong>STAT3 募集与修饰：</strong> 胞质中的 STAT3 通过其 <strong>SH2 结构域</strong> 识别磷酸化的受体位点，并在 <strong>Tyr705</strong> 位点被 JAK 磷酸化。</li><br />
<li style="margin-bottom: 12px;"><strong>二聚化与易位：</strong> 磷酸化的 STAT3 从受体解离，形成同源二聚体，穿过核孔进入细胞核，结合特定的 DNA 启动子序列。</li><br />
</ul><br />
<br />
<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; text-decoration: none;">临床视角：炎症风暴与肿瘤生存</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
STAT3 的失控激活是现代医学面临的两大挑战——急性毒性与肿瘤耐药的交汇点：<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 30%;">病理领域</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">STAT3 的具体作用</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[CRS]] (细胞因子风暴)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">诱导血管内皮活化，驱动肝脏产生 <strong>[[CRP]]</strong> 及铁蛋白。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">管理 [[CAR-T]] 治疗中危及生命的全身炎症。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">肿瘤抗凋亡</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">上调 Bcl-2 和 Survivin，赋予癌细胞生存优势。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">介导化疗及靶向治疗的多药耐药。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">免疫抑制 (TME)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">诱导 <strong>[[M2 极化]]</strong>，抑制树突状细胞成熟。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">构建免疫冷肿瘤，阻断 PD-1 抗体效力。</td><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; text-decoration: none;">前沿干预：从 JAK 抑制到 STAT3 降解</h2><br />
<p style="margin: 15px 0; text-align: justify;"><br />
针对该通路的精准抑制是当前临床转化的热点方向：<br />
</p><br />
<ul style="padding-left: 25px; color: #334155;"><br />
<li style="margin-bottom: 12px;"><strong>JAK 抑制剂：</strong> 鲁索替尼（Ruxolitinib）等 Jakinibs 通过阻断激酶活性，在治疗骨髓纤维化及缓解重症 CRS 中表现卓越。</li><br />
<li style="margin-bottom: 12px;"><strong>STAT3 抑制剂：</strong> 开发针对 SH2 结构域的小分子拮抗剂，旨在直接阻断 STAT3 的二聚化与 DNA 结合。</li><br />
<li style="margin-bottom: 12px;"><strong>[[PROTAC]] 降解：</strong> 利用蛋白降解靶向联合技术，实现对细胞内持续活化的 STAT3 蛋白的彻底清除，克服传统抑制剂的代偿性激活风险。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[1] <strong>Darnell JE, et al. (1994).</strong> <em>Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins.</em> <strong>Science</strong>. <br><br />
<span style="color: #475569;">[学术点评]：通路发现的里程碑研究，确立了 STAT 蛋白作为受体激活后直接入核传递指令的简洁模型。</span><br />
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<p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;"><br />
[2] <strong>Yu H, Jove R. (2004).</strong> <em>The STATs of cancer — new molecular targets come of age.</em> <strong>Nature Reviews Cancer</strong>. <br><br />
<span style="color: #475569;">[学术点评]：系统阐述了 STAT3 在多种实体瘤及血液肿瘤中的促癌活性，定义了其作为抗癌靶点的临床潜力。</span><br />
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<p style="margin: 12px 0;"><br />
[3] <strong>Levy DE, Darnell JE. (2002).</strong> <em>Stats: transcriptional control and biological impact.</em> <strong>Nature Reviews Molecular Cell Biology</strong>. <br><br />
<span style="color: #475569;">[学术点评]：详述了 STAT3 在胚胎发育、器官稳态及炎症反应中的广泛影响，揭示了该通路的生化多样性。</span><br />
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<div style="background-color: #0f172a; color: #ffffff; text-align: center; font-weight: bold; padding: 10px; letter-spacing: 1px;">JAK-STAT3 · 知识图谱关联</div><br />
<div style="padding: 15px; background: #ffffff; line-height: 2.2; text-align: center; text-decoration: none;"><br />
[[IL-6]] • [[gp130]] • [[JAK 激酶]] • [[STAT3]] • [[细胞因子风暴 (CRS)]] • [[抗凋亡机制]] • [[M2 极化]]<br />
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