Summary diagram of JAK/STAT and MAPK signal transduction. (a) To activate JAK/STAT signaling, CNTF binding to the GPI linked CNTFRα initiates recruitment of LIFRβ (L) and GP130 (G) to form the hexameric CNTF receptor complex. Recruited LIFRβ and GP130 are phosphorylated on their cytoplasmic domain by JAK1/2. Activated JAK1/2 phosphorylate STAT3α, which forms homodimers that translocate to the nucleus. pSTAT3 homodimers bind to DNA and activate transcription of target genes, such as Gfap, to initiate gliosis. (b) The MAPK signaling pathway can be activated downstream of ligand binding to receptor tyrosine-kinases (RTKs) by growth factors including HB-EGF, EGF, FGF1, and FGF2 or by activation of CNTFR by CNTF. In both pathways, adaptor proteins such as GBR2 recruit SOS to the activated receptor, and subsequent activation of SOS leads to phosphorylation of RAS, MEK, and finally ERK1/2. Activated ERK1/2 translocate into the nucleus and phosphorylate several transcription factors involved in cell proliferation, cell survival, and cell differentiation.