Here's an abstract of one of the papers inplicating STATs in leptin
signalling (an LGND Scientific Advisory Board member, Jim Darnell, is
widley regarded as the leader in basic research focusing on STATs):
Proceedings of the National Academy of Sciences
Volume 93, Number 13; Pages: 6231-6235
Biochemistry
Defective STAT signaling by the leptin receptor in diabetic mice
Nico Ghilardi, Sandra Ziegler, Adrian Wiestner, Ruedi Stoffel, Markus H.
Heim, Radek C. Skoda
c 1996 by the National Academy of Sciences
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. |
