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Defective STAT signaling by the leptin receptor in diabetic mice.

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Ghilardi, N, Ziegler, S, Wiestner, A, Stoffel, R, Heim, M H, Skoda, R C·1996·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.93.13.6231

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Abstract

Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. Splice variants of OB-R mRNA encode proteins that differ in the length of their cytoplasmic domains. We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. A point mutation within the OB-R gene of diabetic (db) mice generates a new splice donor site that dramatically reduces expression of this long isoform in homozygous db/db mice. In contrast, an OB-R protein with a shorter cytoplasmic domain is present in both db/db and wild-type mice. We show that this short isoform is unable to activate the STAT pathway. These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin.

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Authors: Ghilardi, N., Ziegler, S., Wiestner, A., Stoffel, R., Heim, M. H., & Skoda, R. C.
Venue: Proceedings of the National Academy of Sciences
Publisher: Proceedings of the National Academy of Sciences
Published: 1996-06-25
Volume: 93
Issue: 13
Pages: 6231-6235
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.93.13.6231
OpenAlex: W2044153433
Cited by: 793
References: 4
FWCI: 20.80
Type: journal article
Language: en
Open access: green

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Defective STAT signaling by the leptin receptor in diabetic mice.

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