Constitutive and impaired signaling of leptin receptors containing the Gln → Pro extracellular domain fatty mutation

• DOI: 10.1073/pnas.94.20.10657
• Publication Date: 2002-07-26T14:32:33Z
• Authors: David W. White; Yanping Wang; Streamson C. Chua; J. P. Morgenstern; Rudolph L. Leibel; Heinz Baumann; Louis A. Tartaglia
• Keywords: Leptin receptor; Cytokine receptor

Leptin (OB), an adipocyte-secreted circulating hormone, and its receptor (OB-R) are key components of endocrine loop that regulates mammalian body weight. In this report we have analyzed signal transduction activities OB-R containing the fatty mutation [OB-R( fa )], a single amino acid substitution at position 269 (Gln → Pro) in extracellular domain results obese phenotype rat. We find mutant exhibits both ligand-independent transcriptional activation via interleukin 6 hematopoietin response elements transducer activator transcription (STAT) proteins 1 3. However, OB-R( ) is unable to constitutively activate STAT5B highly impaired for ligand induced compared with wt ). Introduction into OB-R/G-CSF-R chimera generates constitutive character similar but distinct from Constitutive signaling repressed by coexpression The implications generating cytokine partially discussed terms mechanism triggering biology