Ciliary neurotrophic factor actions

Trophic factors exemplified by NGF and its family members, ciliary neurotrophic factor (CNTF) and glial derived neurotrophic factor (GDNF) all utilize increased tyrosine phosphorylation of cellular substrates to mediate neuronal cell survival. Actions of the NGF family of neurotrophins are not only dictated by ras activation through the Trk family of receptor tyrosine kinases, but also a survival pathway defined by phosphatidylinositol-3-kinase activity (Yao and Cooper, 1995), which gives rise to phosphoinositide intermediates that activate the serine/ threonine kinase Akt/PKB (Dudek et al., 1997). Induction of the serine-threonine kinase activity is critical for cell survival, as well as cell proliferation. Hence, for many trophic factors, multiple proteins constitute a functional multisubunit receptor complex that activates rai-depen-dent and ras-independent intracellular signaling. 

Gupta, S.K., Haggarty, A.J., Carbonetto, S., Riopelle, R.J., Richardson, P.M. and Dunn, R.J. (1993) Trophic actions of ciliary neurotrophic factor on murine embryonal carcinoma cells. Eur. J. Neurosci. 5 977-985. 

The actions of ciliary neurotrophic factor have been reviewed recently (Manthorpe et al., 1993). It can support the survival of embryonic sensory neurons in vitro, but not in vivo (Oppenheim et al.,... 

---