Baumann, Faculty Advisor, Heinz

Schoening, Jean

Wang, Yanping

English

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Illinois Wesleyan UniversityDigital Commons @ IWUJohn Wesley Powell Student ResearchConference 1998, 9th Annual JWP ConferenceApr 18th, 11:15 AM - 11:30 AMEffects of the faMutation on the Leptin ReceptorJean SchoeningIllinois Wesleyan UniversityYanping WangIllinois Wesleyan UniversityHeinz Baumann, Faculty AdvisorIllinois Wesleyan UniversityFollow this and additional works at: http://digitalcommons.iwu.edu/jwprcThis Event is brought to you for free and open access by The Ames Library, the Andrew W. Mellon Center for Curricular and FacultyDevelopment, the Office of the Provost and the Office of the President. It has been accepted for inclusion in Digital Commons @ IWU bythe faculty at Illinois Wesleyan University. For more information, please contact digitalcommons@iwu.edu.©Copyright is owned by the author of this document.Schoening, Jean; Wang, Yanping; and Baumann, Faculty Advisor, Heinz, "Effects of the fa Mutation on the LeptinReceptor" (1998). John Wesley Powell Student Research Conference. 4.http://digitalcommons.iwu.edu/jwprc/1998/oralpres3/4Oral Presentation 3 .4 EFFECTS OF THE fa MUTATTION ON THE LEPTIN RECEPTOR Jean Schoening, Yanping Wang, and Heinz Baumann* Department of Biology, illinois Wesleyan University and Department of Molecular and Cellular Biology, Roswell Park Cancer Institiute Leptin, a honnone released by adipocytes and involved in the regulation of energy, binds to the leptin receptor (OB_R.)l The activated OB-R induces the phosphorylation of the receptor itself and Janus kinases OAKs) . The JAKs. then activate Signal Transducer and Activator of Transcription (STAT) proteins which translocate to the nucleus to regulate genes. A result of a single amino acid substitution, the fatty mutation of OB-R (OB-R(fa)) is found in the extracellular domain of the receptor. This mutation leads to an obese phenotype in homozygous fa/fa rats.2 Preliminary experiments suggest that the fatty mutation may cause deficiences in the signal transducing capabilities of the receptor.3 The goal of this study was to identify the precise signaling function of the OB-R(fa) . Human kidney 293 cells were generated that stably express either the wild type OB-R (OB-R(wt)) or OB-R(fa) . These stable cells exhibited significantly increased ligand binding relative to the parental cell line. When treated with leptin, both OB-R(wt) and OB-R(fa) cells indicate an increase in STATI and STAT3 activity. The OB-R(fa) cells exhibit an increase in the basal level of DNA binding activity in the absence of leptin. The constitutive activity of OB-R(fa) was verified with gene induction experiments. In addition, leptin treatment also activiates the SHP-2 protein tyrosine phosphatase, which is predicted to down-regulate OB-R signaling . This finding is in contrast to the previous report that suggested SHP-2 is not part of OB-R signaling.4 These results demonstrate that OB-R(fa) alters the function of the receptor by introducing a ligand-independent signal transduction, suggesting that the fatty phenotype is mechanistically distinct from the diabetes mutation of OB-R which causes a signal incompetent receptor.t,7 References:  1. Tartaglia, L.  (1997) J. BioI. Chern. 272, 6093-6096. 2. Chua, S., et. al. (1996) Diabetes, 45, 1141-1143. 3. Yamashita, T., et. al. (1997) Diabetes, 46, 1077-1080. 4. Nakashima, K., et. al. (1997) FEBS, 401, 49-52. 5. Wang, Y., et. al. (1997) J. Bioi. Chern., 272, 16216-16223 . 6 .  White, D ., et. al. (1997) J. BioI. Chern., 272, 4065-4071. 7. Baumann, H., et. al . (1996) Proc. Natl. Acad. Sci. U.S.A,. 93, 8374-8376. 

Effects of the \u3cem\u3efa\u3c/em\u3e Mutation on the Leptin Receptor

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Effects of the \u3cem\u3efa\u3c/em\u3e Mutation on the Leptin Receptor

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