The neuron-glia signal β neuregulin induces sustained CREB phosphorylation on Ser-133 in cultured rat Schwann cells

被引:34
作者
Tabernero, A [1 ]
Stewart, HJS [1 ]
Jessen, KR [1 ]
Mirsky, R [1 ]
机构
[1] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England
基金
英国惠康基金; 英国医学研究理事会;
关键词
PNS; sciatic nerve; cAMP; SMDF; neu differentiation factor; heregulin;
D O I
10.1006/mcne.1998.0662
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
beta neuregulins (also called NDF, GGF, ARIA, and heregulins) are neuron-derived molecules that are likely to be responsible for Schwann cell precursor survival, proliferation, and maturation in vivo and in vitro. although the receptors to which beta neuregulins bind have been defined, little is known about the transcription factors these important ligands activate. Using antibodies, quantitative imaging methods and Western blotting, we show that beta neuregulin induces a high level of phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB) on Ser-133 in cultured rat Schwann cells and that the phosphorylation is prolonged over several hours. In contrast, neurotrophins, CNTF, FGF-2, EGF, and TGF beta induce little or no phosphorylation of CREB despite the fact that receptors for these factors are present on Schwann cells. As expected CREB phosphorylation was detected following cAMP elevation, and it was also Induced by elevation of cytoplasmic Ca(2+), endothelin 1, and PDGF-BB. The signal was lower than that seen in response to beta neuregulin, and transient, unlike the sustained CREB activation induced by beta neuregulin. Our results suggest that the sustained phosphorylation of CREB on Ser-133 may contribute to the broad spectrum of effects that beta neuregulins have on cells of the Schwann cell lineage and that the CREB pathway may be important for transduction of neuregulin signals in Schwann cells.
引用
收藏
页码:309 / 322
页数:14
相关论文
共 59 条
[1]   EXPRESSION OF A PEPTIDE INHIBITOR OF PROTEIN PHOSPHATASE-1 INCREASES PHOSPHORYLATION AND ACTIVITY OF CREB IN NIH 3T3 FIBROBLASTS [J].
ALBERTS, AS ;
MONTMINY, M ;
SHENOLIKAR, S ;
FERAMISCO, JR .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (07) :4398-4407
[2]   PD-098059 IS A SPECIFIC INHIBITOR OF THE ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE KINASE IN-VITRO AND IN-VIVO [J].
ALESSI, DR ;
CUENDA, A ;
COHEN, P ;
DUDLEY, DT ;
SALTIEL, AR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (46) :27489-27494
[3]  
BENBARUCH N, 1994, P SOC EXP BIOL MED, V206, P221
[4]   SERINE 133-PHOSPHORYLATED CREB INDUCES TRANSCRIPTION VIA A COOPERATIVE MECHANISM THAT MAY CONFER SPECIFICITY TO NEUROTROPHIN SIGNALS [J].
BONNI, A ;
GINTY, DD ;
DUDEK, H ;
GREENBERG, ME .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1995, 6 (02) :168-183
[5]  
BROCKES JP, 1980, J BIOL CHEM, V255, P8374
[6]   GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors [J].
Canoll, PD ;
Musacchio, JM ;
Hardy, R ;
Reynolds, R ;
Marchionni, MA ;
Salzer, JL .
NEURON, 1996, 17 (02) :229-243
[7]   Cultured schwann cells constitutively express the myelin protein P-0 [J].
Cheng, LL ;
Mudge, AW .
NEURON, 1996, 16 (02) :309-319
[8]   EXPRESSION OF THE NEU PROTOONCOGENE BY SCHWANN-CELLS DURING PERIPHERAL-NERVE DEVELOPMENT AND WALLERIAN DEGENERATION [J].
COHEN, JA ;
YACHNIS, AT ;
ARAI, M ;
DAVIS, JG ;
SCHERER, SS .
JOURNAL OF NEUROSCIENCE RESEARCH, 1992, 31 (04) :622-634
[9]   NEU DIFFERENTIATION FACTOR IS A NEURON-GLIA SIGNAL AND REGULATES SURVIVAL, PROLIFERATION, AND MATURATION OF RAT SCHWANN-CELL PRECURSORS [J].
DONG, Z ;
BRENNAN, A ;
LIU, N ;
YARDEN, Y ;
LEFKOWITZ, G ;
MIRSKY, R ;
JESSEN, KR .
NEURON, 1995, 15 (03) :585-596
[10]  
DONG Z, 1997, GLIA, V20, P1