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CTLA-4

CTLA-4. Inhibitory signal. Inhibitory signal. Activator signal. SHP-1/2. PD1. Up “28 kinases”. Up “supervised list”. KIR. DAP10. Anti-tumor mediated activation. NKG2D. PLC- . Pi3K. Activation signal. 1. PIP(3-5)P3. CD28. LCK. Pyk2. TCR/NCR or BCR mediated activation. ZAP-70.

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CTLA-4

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  1. CTLA-4 Inhibitory signal Inhibitory signal Activator signal SHP-1/2 PD1 Up “28 kinases” Up “supervised list” KIR DAP10 Anti-tumor mediated activation NKG2D PLC- Pi3K Activation signal 1 PIP(3-5)P3 CD28 LCK Pyk2 TCR/NCR or BCR mediated activation ZAP-70 Rho/ CDC42 Vav LCP2 FAK Syk Fyn TCR CD3 GADS LAT 2 CD3 Rac ERK1/2 Movement & granules exocytosis Proliferation Differentiation/cytotoxicity Immune response/Activation Grb2 ITK Apoptosis of targeted cells MAPK signaling pathway AP1 SOS RAS PLC- Cell survival PIM2 NFKB FASL RASGRP1/2 Bid CASP IKKa CARMA1 DAG PKC IKKg BCL10 IKB IKKb MALT1 PRF1, GZM, GNLY, CMK, FASL… Ca2+ signaling pathway CTK regulation Ca2+ release IP3 NFAT GZM PERF GZM Movement & exocytosis Cytokine mediated activation 3 CTK-R JAK-STAT signaling pathway IFNs-R TRAIL Figure S1

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