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Front Immunol：研究发现磷脂酰丝氨酸是Gas6的TAM活化必不可少的

2017-12-03 MedSci MedSci原创

Gas6TAM磷脂酰丝氨酸
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Tyro3、Axl和Mertk（TAM）受体是同源I型受体酪氨酸激酶，在多细胞生物体中凋亡细胞的清除中具有关键作用。TAMs被其内源性配体/生长抑制特异性6（Gas6）和蛋白S（Pros1）激活，其在凋亡细胞上外化的磷脂酰丝氨酸（PS）与TAM胞外域之间起桥接分子的作用。然而，Gas6/Pros1促进TAM活化的分子机制仍尚未清楚。本研究中，研究人员使用TAM/IFNγR1报告细胞系监测功能性TA

Tyro3、Axl和Mertk（TAM）受体是同源I型受体酪氨酸激酶，在多细胞生物体中凋亡细胞的清除中具有关键作用。TAMs被其内源性配体/生长抑制特异性6（Gas6）和蛋白S（Pros1）激活，其在凋亡细胞上外化的磷脂酰丝氨酸（PS）与TAM胞外域之间起桥接分子的作用。然而，Gas6/Pros1促进TAM活化的分子机制仍尚未清楚。

本研究中，研究人员使用TAM/IFNγR1报告细胞系监测功能性TAM的活性，结果发现Gas6活性完全依赖于维生素K介导的γ-羧化作用，由此用抗凝剂华法林代替维生素K，或者通过代替参与PS结合的谷氨酸残基，完全取消Gas6活性作为TAM配体。此外，使用结构域和点诱变，Gas6活性还需要完整的Gla结构域和完整的EGF样结构域，这表明这些结构域协同工作以实现TAM的活化。尽管需要γ-羧基化和功能性Gla结构域，非γ-羧基化的Gas6和Gla缺失/EGF-样结构域缺失突变体仍然保留其结合TAM并作为阻断性诱骗配体的能力。最后，研究人员发现，PS-阳性细胞/囊泡（包括凋亡细胞、钙诱导的应激细胞和外泌体）的不同来源与Gas6结合并作为细胞来源或外泌体来源的配体激活TAMs。

综上所述，我们的研究结果表明，PS对于Gas6的TAM活化是必不可少的，并推出PS如何调节TAM受体和胞吞作用的新观点。

原始出处：

Geng K, Kumar S, et al., Requirement of Gamma-Carboxyglutamic Acid Modification and Phosphatidylserine Binding for the Activation of Tyro3, Axl, and Mertk Receptors by Growth Arrest-Specific 6. Front Immunol. 2017 Nov 10;8:1521. doi: 10.3389/fimmu.2017.01521. eCollection 2017.

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    2018-01-21 许安

    #GAS#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=2071989, encodeId=475920e19899f, content=<a href='/topic/show?id=9d4ee84647' target=_blank style='color:#2F92EE;'>#GAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7846, encryptionId=9d4ee84647, topicName=GAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sun Jan 21 10:56:00 CST 2018, time=2018-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753348, encodeId=c3b31e5334847, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Sat Sep 08 13:56:00 CST 2018, time=2018-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968561, encodeId=31f41968561ea, content=<a href='/topic/show?id=2e902103631' target=_blank style='color:#2F92EE;'>#丝氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21036, encryptionId=2e902103631, topicName=丝氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Tue Jan 09 23:56:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=268583, encodeId=0ae5268583a6, content=很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib2emBzjO0FtqTJ05AqrEEdRmp6tmlsLXqpzfxWdtgbbgPGWRHagoK9fLTd3IayRPgkJVIVBWtdlmnkBhOIR4cFM/0, createdBy=e8d51649330, createdName=飘飘爱, createdTime=Mon Dec 11 11:50:02 CST 2017, time=2017-12-11, status=1, ipAttribution=)]
    2018-09-08 hanhaisha2020

    #研究发现#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2071989, encodeId=475920e19899f, content=<a href='/topic/show?id=9d4ee84647' target=_blank style='color:#2F92EE;'>#GAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7846, encryptionId=9d4ee84647, topicName=GAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sun Jan 21 10:56:00 CST 2018, time=2018-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753348, encodeId=c3b31e5334847, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Sat Sep 08 13:56:00 CST 2018, time=2018-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968561, encodeId=31f41968561ea, content=<a href='/topic/show?id=2e902103631' target=_blank style='color:#2F92EE;'>#丝氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21036, encryptionId=2e902103631, topicName=丝氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Tue Jan 09 23:56:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=268583, encodeId=0ae5268583a6, content=很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib2emBzjO0FtqTJ05AqrEEdRmp6tmlsLXqpzfxWdtgbbgPGWRHagoK9fLTd3IayRPgkJVIVBWtdlmnkBhOIR4cFM/0, createdBy=e8d51649330, createdName=飘飘爱, createdTime=Mon Dec 11 11:50:02 CST 2017, time=2017-12-11, status=1, ipAttribution=)]
    2018-01-09 jiangjun073

    #丝氨酸#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2071989, encodeId=475920e19899f, content=<a href='/topic/show?id=9d4ee84647' target=_blank style='color:#2F92EE;'>#GAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7846, encryptionId=9d4ee84647, topicName=GAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sun Jan 21 10:56:00 CST 2018, time=2018-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1753348, encodeId=c3b31e5334847, content=<a href='/topic/show?id=6a57e33772b' target=_blank style='color:#2F92EE;'>#研究发现#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73377, encryptionId=6a57e33772b, topicName=研究发现)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7e1736602208, createdName=hanhaisha2020, createdTime=Sat Sep 08 13:56:00 CST 2018, time=2018-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1968561, encodeId=31f41968561ea, content=<a href='/topic/show?id=2e902103631' target=_blank style='color:#2F92EE;'>#丝氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=21036, encryptionId=2e902103631, topicName=丝氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=jiangjun073, createdTime=Tue Jan 09 23:56:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=268583, encodeId=0ae5268583a6, content=很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib2emBzjO0FtqTJ05AqrEEdRmp6tmlsLXqpzfxWdtgbbgPGWRHagoK9fLTd3IayRPgkJVIVBWtdlmnkBhOIR4cFM/0, createdBy=e8d51649330, createdName=飘飘爱, createdTime=Mon Dec 11 11:50:02 CST 2017, time=2017-12-11, status=1, ipAttribution=)]
    2017-12-11 飘飘爱

    很好

    0