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JAKÒÖÖÆ¼ÁÖ÷ÒªÓÃÓÚÖÎÁÆÑªÒºÏµÍ³¼²²¡¡¢¡¢Ö×Áö¡¢¡¢Àà·çʪÐÔÊàŦÑ×¼°ÒøÐ¼²¡µÈ¼²²¡£¬£¬£¬·ÅÑÛÈ«ÇòºÍº£ÄÚ£¬£¬£¬JAKÒÖÖÆ¼ÁÓÈÆäÊǵڶþ´úJAKÒÖÖÆ¼ÁµÄÑз¢´¦ÓÚ»ðÈȽ׶Σ¬£¬£¬ÆäÖÐ×îÒªº¦µÄ»·½ÚÊÇÔõÑù¾«×¼¡¢¡¢¸ßЧɸѡ³ö¸ßÑ¡ÔñÐÔµÄJAKÒÖÖÆ¼Á¡£¡£¡£Îª´Ë£¬£¬£¬GA»Æ½ð¼×¿ª·¢ÁËJAKÒÖÖÆ¼ÁµÄÖÜÈ«ÆÀ¼Ûϵͳ£¬£¬£¬°üÀ¨Ba/F3¼¤Ã¸°Ðµã¹¤³Ìϸ°ûÖê¡¢¡¢»ùÓÚELISA, Phosho-Flow£¬£¬£¬AlphaELISA¼ì²âµÄȫѪ/ϸ°ûϵ/Tϸ°û·Ö»¯µÈÆÀ¼Ûƽ̨£¬£¬£¬×ÊÖú¿Í»§Ìá¸ßÐÂÒ©Ñз¢×¼È·ÂʺÍЧÂÊ¡£¡£¡£

 

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¹ØÓÚJAK¼¤Ã¸¼°JAK-STATÐźÅͨ·

JAK¼Ò×å

Janus Kinase(JAK)ÊÇÒ»Àà°ûÄÚ·ÇÊÜÌåÀÒ°±Ëἤø£¬£¬£¬JAK¼Ò×åÓÐ4¸ö³ÉÔ±£ºJAK1¡¢¡¢JAK2¡¢¡¢JAK3ºÍTYK2¡£¡£¡£JAK1¡¢¡¢JAK2ºÍTYK2ÆÕ±é±£´æÓÚÈËÌ壬£¬£¬¶øJAK3Ö÷Òª±£´æÓÚ¹ÇËèϸ°û¡¢¡¢ÐØÏÙϸ°ûºÍÃâÒßϸ°ûÖС£¡£¡£

µ±´Ì¼¤Òò×ÓÓëÏìÓ¦ÊÜÌåÁ¬Ïµºó£¬£¬£¬ÒýÆðÊÜÌ屬·¢¾Û»¯£¬£¬£¬Ê¹µÃÓëÊÜÌåżÁªµÄJAK¼¤Ã¸Ï໥¿¿½ü£¬£¬£¬´ß»¯ÊÜÌåÉϵÄTyr²Ð»ù±¬·¢Á×Ëữ£¬£¬£¬½øÒ»²½ÕÐļÖÜΧSTATÂѰ×£¬£¬£¬¼Ì¶øJAK¼¤Ã¸´ß»¯Á¬ÏµÔÚÊÜÌåÉϵÄSTAT±¬·¢Á×Ëữ²¢¼¤»î£¬£¬£¬×îºóÒÔ¶þ¾ÛÌåµÄÐÎÊ½×ªÒÆÖÁϸ°ûºËÄÚ£¬£¬£¬µ÷¿ØÏìÓ¦µÄ°Ð»ùÒòת¼ºÍ±í´ï(ͼ1)¡£¡£¡£

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ͼ1. JAK¼¤Ã¸¼ò½é

(ͼƬȪԴ£º×óͼȪԴÓڲο¼×ÊÁÏ[1])

 

JAK-STATÐźÅͨ·

JAK¼¤Ã¸ÓëÐźÅתµ¼¼°×ªÂ¼¼¤»îÂѰ×(Singal transducers and activators of transcription, STAT)Ö®¼äµÄÏ໥×÷ÓÃÔÚϸ°ûÒò×Ó¡¢¡¢¼¤Ëؼ°Ç÷»¯Òò×ÓµÈÊÜÌåÐźÅͨ·ÖÐʩչ×ÅÖ÷Òª×÷Ó㬣¬£¬Èç°×½éËØ¡¢¡¢×ÌÈÅËØºÍ¼¯Âä´Ì¼¤Òò×ӵȡ£¡£¡£Òò´Ë£¬£¬£¬JAK-STATÐźÅͨ·¹¦Ð§ÆÕ±é£¬£¬£¬¼ÓÈëϸ°ûµÄÔöÖ³¡¢¡¢·Ö»¯ÒÔ¼°ÃâÒßµ÷ÀíµÈÖî¶àÖ÷ÒªµÄÉúÎïѧÀú³Ì£¨Í¼2£©£¬£¬£¬µ«JAK¼¤Ã¸Ì«¹ý»î»¯»áµ¼ÖÂÑ×Ö¢µÈ¼²²¡µÄ±¬·¢¡£¡£¡£

 
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ͼ2. JAK-STATͨ·¼ÓÈëµÄϸ°ûÖÖÖÖÉúÎïѧÀú³Ì(ͼƬȪԴ£º²Î¿¼×ÊÁÏ[2])

 

 

JAKÒÖÖÆ¼ÁÑз¢Ç÷ÊÆ

×÷ΪҩÎï°Ðµã¿ª·¢ÒÔÀ´£¬£¬£¬JAKÒѾ­×ß¹ýÁ˽ü30ÄêµÄ·çÓêÀú³Ì£¬£¬£¬³ÉΪÑ×Ö¢¡¢¡¢×ÔÉíÃâÒß²¡¡¢¡¢°©Ö¢µÈÁìÓòµÄÈÈÃŰе㣬£¬£¬Èçͼ3Ëùʾ¡£¡£¡£JAKÒÖÖÆ¼Á³ýÁËÔÚÀà·çʪÊàŦÑ×ÖÐÁÆÐ§Í»³öÍ⣬£¬£¬ÉÐÓжàÖÖ˳Ӧ֢±»Åú»ò´¦ÓÚÁÙ´²Ñо¿½×¶Î£¬£¬£¬°üÀ¨£º¹ÇËèÔöÉúÐÔÖ×Áö¡¢¡¢ÒÆÖ²ÎËÞÖ÷²¡¡¢¡¢ÒøÐ¼²¡ÊàŦÑס¢¡¢Ñ×Ö¢ÐÔ³¦²¡¡¢¡¢ºì°ßÀÇ´¯ºÍǿֱ¼¹ÖùÑ׵ȡ£¡£¡£

 

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ͼ3. JAK²î±ðÑÇÐÍÂþÑܼ°ÏìÓ¦ÒÖÖÆ¼Á

(ͼƬȪԴ£º²Î¿¼×ÊÁÏ[1])

 

GA»Æ½ð¼×Ϊ¿Í»§ÌṩÖÜÈ«JAKÒÖÖÆ¼ÁÆÀ¼Ûϵͳ

 

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PARTIAL DATA

1¡¢¡¢Ba/F3-TEL-JAK1ϸ°ûÔöֳʵÑéÊý¾Ý

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2¡¢¡¢Ba/F3-EPOR-JAK2-V617Fϸ°ûÔöÖ³¼°ÌåÄÚҩЧʵÑéÊý¾Ý

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3¡¢¡¢Ba/F3-FL-TYK2£¨È«³¤ÐòÁУ©ÊÔÑéÊý¾Ý±ÈÕÕ

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ÓÒͼ£ºÊ¹ÓÃGA»Æ½ð¼×¹¹½¨µÄBa/F3-FL-TYK2(JH1 JH2)ϸ°û¿ÉÒÔÖ±½Ó¼ì²âBMS-986165µÈ±ä¹¹¼Á¶Ôϸ°ûÔöÖ³µÄÒÖÖÆ»îÐÔ¡£¡£¡£

 

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[1]SCHWARTZ D M, KANNO Y, VILLARINO A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases [J]. Nature Reviews Drug Discovery, 2017, 16(12): 843-62.

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