STAT1 Ser727 – key regulator for NK cell-mediated cytotoxicity and tumor surveillance

• DOI: 10.1186/1471-2210-8-s1-a27
• Publication Date: 2008-11-05T20:32:02Z
• Authors: Eva M Putz; Eva Zebedin-Brandl; Michaela Prchal; Thomas Decker; Pavel Kovarik; Veronika Sexl
• Keywords: Pharmacology; 0303 health sciences; 03 medical and health sciences; Meeting Abstract; Pharmacology (medical); 3. Good health

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade plays an important role in hematopoiesis. A constitutive activation this pathway is found a broad variety diverse human murine leukemias lymphomas. Whereas STAT3 STAT5 accelerate initiate tumor formation, STAT1 generally considered suppressor. As shown by Kovacic et al. [1], accelerates leukemia formation up-regulation MHC class I on leukemic cells allowing them to escape natural killer (NK) cell-mediated lysis. In the present study we investigate serine727 phosphorylation site for initiation progression. After retroviral induction STAT1S727A knock-in mice show enhanced disease latency compared wild type (WT) mice. Upon injection B16 melanoma cells, numbers lung metastases were increased STAT1-/- recipients, but significantly reduced when WT This indicates that effect may not be cell-intrinsic rather results from altered interactions with host immune system. Clearance mainly mediated NK cells. Therefore, differences might explain our vivo data. determined [3H]thymidine incorporation assay, showed proliferation rates Moreover, classical [51Cr]-release assay able lyse more efficiently than can divided into different functional subsets according cell surface expression DX5, Mac-1 CD27. Ex fluorescence-activated sorting (FACS)-based analysis revealed distinct pattern (Mac-1+, DX5+, CD27+), characteristic pre-activated phenotype [2] spite absence any activating stimulus. These experiments indicate relevant activation, cytolytic function as consequence their ability eradicate vivo.