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Transregulation of leukemia inhibitor factor receptor expression and function by growth factors in neuroblastoma cells
Author(s) -
Port Martha D.,
Laszlo George S.,
Nathanson Neil M.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05535.x
Subject(s) - leukemia inhibitory factor receptor , leukemia inhibitory factor , microbiology and biotechnology , signal transduction , biology , mapk/erk pathway , cancer research , platelet derived growth factor receptor , growth factor receptor inhibitor , tropomyosin receptor kinase c , growth factor receptor , growth factor , cytokine , receptor , immunology , biochemistry , interleukin 6
The cytokines that signal through the leukemia inhibitory factor (LIF) receptor are members of the neuropoietic cytokine family and have varied and numerous roles in the nervous system. In this report, we have determined the effects of growth factor stimulation on LIF receptor (LIFR) expression and signal transduction in the human neuroblastoma cell line NBFL. We show here that stimulation of NBFL cells with either epidermal growth factor or fibroblast growth factor decreases the level of LIFR in an extracellular signal‐regulated kinase (Erk)1/2‐dependent manner and that this down‐regulation is due to an increase in the apparent rate of lysosomal LIFR degradation. Growth factor‐induced decreases in LIFR level inhibit both LIF‐stimulated phosphorylation of signal transducers and activators of transcription 3 and LIFR‐mediated gene induction. We also show that Ser1044 of LIFR, which we have previously shown to be phosphorylated by Erk1/2, is required for the inhibitory effects of growth factors. Neurons are exposed to varying combinations and concentrations of growth factors and cytokines that influence their growth, development, differentiation, and repair in vivo . These findings demonstrate that LIFR expression and signaling in neuroblastoma cells can be regulated by growth factors that are potent activators of the mitogen‐activated protein kinase pathway, and thus illustrate a fundamental mechanism that underlies crosstalk between receptor tyrosine kinase and neuropoietic cytokine signaling pathways.