LEUKEMIA inhibitory factor (LIF) is a member of a family of neuropoiet
ic cytokines which influence neuronal survival, differentiation and re
sponse to injury. In cell lines LIF activates the Jak/Tyk tyrosine kin
ases and the STAT family of transcription factors. We have investigate
d whether the Jak-STAT intracellular signaling pathway is activated by
LIF after neuronal injury in vivo. Axotomy of postganglionic sympathe
tic nerves resulted in sustained activation of members of the STAT tra
nscription factor family, This activation is dependent on LIF as axoto
my failed to activate STAT proteins in LIF-deficient mice. These data
indicate that LIF-dependent activation of STAT proteins is one of the
signal transduction pathways activated after neuronal injury.