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?qGTP ? ? NO – mediated attenuation of adrenergic Gq signaling in VSMC ?q GDP ? ? PLC? ?qGTP Ca sGC cGMP pGC ANP SERCA BKCa PKG PKC MLCK myosin myosin myosin P P CaM MLCK Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca K+ Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca Ca CaM Ca PA 1,4,5-Ins P 精选 ?SGTP ? ? RGS function and regulation ?S GDP ? ? AC PKA cAMP cAMP cAMP cAMP cAMP cAMP cAMP AC ?SGTP Ligand Ligand RGS RGS RGS 14-3-3 RGS P 14-3-3 P cAMP cAMP cAMP TNF? 精选 Modular Structure of Cytokine Receptors IFN?R2515 aa IFN?R1 530 aa IL-6R 449 aa IL-11R 400 aa IL-10R1 557 aa IL-10R2325 aa STATbinding IL-13R?1 427 aa IL-4R? 825 aa FN III FN III CCCC WS-WS FN III FN III FN III FN III FN III FN III FN III FN III FN III FN III SOCS gp130 896 aa STATbinding Tyk2 Jak1 INF?R1 489 aa STATbinding FN III FN III Jak1 IL-22R1 574 aa STATbinding FN III FN III Jak1 Jak1 INF?R2 332 aa FN III FN III Jak2 STATbinding Tyk2 Jak1 Jak2 Jak1 IL-13R?2 380 aa FN III FN III CCCC WS-WS FN III FN III CCCC WS-WS FN III FN III FN III STATbinding STATbinding Ig Ig Ig Ig OSM?-R952 aa Jak3 FN III FN III FN III FN III STATbinding Ig FN III FN III CCCC WS-WS FN III FN III CCCC WS-WS FN III FN III CCCC WS-WS LIF-R? 1053 aa Jak3 FN III FN III FN III STATbinding Ig FN III WS-WS FN III FN III CCCC WS-WS STATbinding STATbinding SHP FN III CCCC STATbinding STATbinding Tyk2 FN III FN III CCCC WS-WS Ig SOCS SHP FN III FN III CCCC WS-WS Ig Jak3 ?c 349 aa IRS FN III FN III CCCC WS-WS Ig Jak3 FN III FN III FN III FN III FN III CCCC WS-WS IL-12? 662 aa FN III WS-WS SOCS IRS STATbinding Ig Tyk2 Fibronectintype III domain Ig - like IRS-binding Fibronectintype III domainwith cysteines SOCS-binding STAT-binding JAK/TYK-binding Fibronectintype III domainwith WSXWS SHP-binding SHP 精选 Adaptor proteins - selected (human) SAM domain Src-homology 3 domain SH3 SH2 Src-homology 2 d