ISOLATION OF IL-2 RECEPTOR-BETA CDNA CLONES FROM ATT-20 PITUITARY-CELLS - CONSTITUTIVE EXPRESSION AND ROLE IN SIGNAL-TRANSDUCTION

Interleukin-2 (IL-2) has been shown to stimulate ACTH secretion by ant erior pituitary cells and has been implicated in pathophysiological pr ocesses of the pituitary and brain in several major neuropsychiatric d isorders. The present study tested the hypothesis that IL-2 receptor-b eta (IL-2R beta), a constitutively expressed and essential subunit for IL-2 signaling in lymphocytes, is expressed by AtT-20 pituitary cells and involved in transducing intracellular signals induced by IL-2. We isolated and sequenced three overlapping IL-2R beta cDNA clones from AtT-20 pituitary cells representing key regions of the gene protein co ding sequence. These cDNA clones included conserved sequences shared b y growth hormone and prolactin as well as intracytoplasmic Src and JAK family homology domains of nonreceptor protein tyrosine kinases essen tial for IL-2 signaling in lymphocytes. Their nucleotide sequences wer e 100% homologous with those expressed by lymphocytes (together they c omprised 70% of the full length coding sequence). The IL-2R beta gene is constitutively expressed by AtT-20 pituitary cells, and its transcr iption was upregulated after CRF stimulation. Species-specific IL-2 in duced intracellular signals in AtT-20 cells known to be mediated by IL -2R beta, including a transient increase in c-myc nuclear proto-oncoge ne transcription and the dose-dependent induction of DNA replication a s measured by [H-3]thymidine incorporation. The IL-2-induced DNA repli cation signal was not delivered by heat inactivated IL-2 and was parti ally blocked by a murine anti-IL-2R beta monoclonal antibody. These st udies suggest that IL-2R beta may be a critical target involved in med iating the neuroimmunological actions of this prototypical cytokine in endocrine cells. (C) 1997 American College of Neuropsychopharmacology . Published by Elsevier Science Inc.