STAT6 is abundantly expressed in 3T3-L1 preadipocytes and adipocytes but ac
tivating ligands are not well defined. In this report, we provide evidence
that interleukin 4 (IL-4) induced JAK2-mediated STAT6 tyrosine phosphorylat
ion and DNA binding in 3T3-L1 preadipocytes but not in 3T3-L1 adipocytes. L
oss of IL-4-mediated STAT6 tyrosine phosphorylation occurred 2 days after p
readipocytes were induced to differentiate into adipocytes but when cells r
emained phenotypically preadipocytes. 3T3-L1 adipocytes were still responsi
ve to IL-4 through tyrosine phosphorylation of other cellular proteins. We
conclude that IL-4 signals through STAT6 in 3T3-L1 preadipocytes but not in
3T3-L1 adipocytes. This differentiation-dependent loss of STAT6 activation
may be critical for distinct biological effects of IL-4 in 3T3-L1 preadipo
cytes and adipocytes. (C) 2000 Academic Press.