Effect of Janus kinase 3 on the peptide transporters PEPT1 and PEPT2

摘要: The tyrosine kinase Janus 3 (JAK3) contributes to signaling regulating the proliferation and apoptosis of lymphocytes tumor cells. Replacement lysine by alanine in catalytic subunit yields inactive (K851A)JAK3 mutant that underlies severe combined immune deficiency. gain-of-function mutation (A572V)JAK3 is found acute megakaryoplastic leukemia T cell lymphoma. excessive nutrient demand cells requires upregulation transporters membrane including peptide PEPT1 PEPT2. carriers further accomplish intestinal transport. Little known about present study explored whether PEPT2 are upregulated JAK3. or was expressed Xenopus oocytes with without additional expression JAK3, electrogenic (glycine-glycine) transport determined dual-electrode voltage clamp. PEPT2-HA protein abundance analyzed chemiluminescence. Intestinal estimated from peptide-induced current Ussing chamber experiments. In PEPT1- PEPT2-expressing oocytes, but not water-injected dipeptide gly-gly generated an inward current, which significantly increased following coexpression effect JAK3 on mimicked (A568V)JAK3 (K851A)JAK3. maximal PEPT1-expressing rather decreased apparent affinity carrier. Coexpression enhanced membrane. JAK3- blunted inhibitor WHI-P154, 4-[(3'-bromo-4'-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline (22 μM). segments a smaller JAK3-deficient mice (jak3⁻/⁻) than wild-type (jak3⁺/⁺). conclusion, powerful regulator