Transregulation of leukemia inhibitor factor receptor expression and function by growth factors in neuroblastoma cells

• Published in: Journal of neurochemistry Vol. 106; no. 4; pp. 1941 - 1951
• Main Authors: Port, Martha D., Laszlo, George S., Nathanson, Neil M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2008; Blackwell
• Subjects: Biochemistry; Biological and medical sciences; cytokine; Cytokines; glycoprotein 130; growth factor; Hematologic and hematopoietic diseases; Leukemia; leukemia inhibitory factor; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; mitogen-activated protein kinase; Neurology; Signal transduction; Tumors of the nervous system. Phacomatoses; Human; Fibroblast growth factor; Nervous system diseases; Extracellular signal-regulated protein kinase; Enzyme; Leukemia; Cytokine; Nervous system; Malignant hemopathy; Malignant tumor; Neuroblastoma; glycoprotein 130; mitogen-activated protein kinase; Signal transduction; Growth factor receptor; Epidermal growth factor; Cell line; Autonomic neuropathy; leukemia inhibitory factor; Cancer; Growth factor; Biological receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05535.x

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.