Expression of galectin-3 in neuronally differentiating PC12 cells is regulated both via Ras/MAPK-dependent and -independent signalling pathways.
Galectin-3 (gal-3) is a member of the galectin family of lectins whose expression strongly depends on the cellular state. Here we show that in PC12 cells the expression of gal-3 protein is regulated via Ras- and mitogen-activated protein kinase (MAPK)-dependent and independent signalling pathways and correlates with nerve growth factor (NGF)-mediated neuronal differentiation. Gal-3 expression, activation of the MAPK ERK1/2 and neurite outgrowth are induced by NGF and basic fibroblast growth factor (bFGF), but not by ciliary neurotrophic factor (CNTF), epidermal growth factor, insulin or interleukin-6 (IL-6). In addition, in NGF-treated PC12 cells, gal-3 expression, ERK1/2 activation and neurite outgrowth could be specifically inhibited at the level of TrkA, Ras and MAPK-kinase, whereas expression of an oncogenic form of Ras leads to gal-3 expression and neurite outgrowth in the absence of growth factors. In NGF-primed PC12 cells, subsequent treatment with CNTF or IL-6 induces ERK1/2 activation and neurite outgrowth, but not gal-3 expression. Treatment of PC12 cells with staurosporine induces gal-3 expression and neurite outgrowth without ERK1/2 activation. NGF- and staurosporine-induced gal-3-expression is also regulated at the transcriptional level. Our data suggest the presence of complex induction mechanisms of gal-3 expression in neuronally differentiating PC12 cells involving NGF-, but not CNTF- and IL-6-driven (in NGF-primed cells) Ras/MAPK-related signalling pathways. Staurosporine, in contrast, induces gal-3 expression by a Ras/MAPK-independent mechanism.
Kuklinski
Stephan
S
Department of Biochemistry, Institute of Animal Anatomy and Physiology, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany.
Vladimirova
Valentina
V
Waha
Andreas
A
Kamata
Hideaki
H
Pesheva
Penka
P
Probstmeier
Rainer
R
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D037502:Galectin 3 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000737:chemistry; D018631:ras Proteins / Q000378:metabolism*
D020934:Ciliary Neurotrophic Factor; D004791:Enzyme Inhibitors; D037502:Galectin 3; D015850:Interleukin-6; D016222:Fibroblast Growth Factor 2; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins