STATus and Context within the Mammalian Nervous System

Abstract

Effective manipulation of human disease processes may be achieved by understanding transcriptional, posttranscriptional and epigenetic events that orchestrate cellular events. The levels of activation of specific molecules, spatial distribution and concentrations of relevant networks of signaling molecules along with the receptiveness of the chromatin to these signals are some of the parameters which dictate context. Effects elicited by the transcription factor signal transducers and activator of transcription 3 (Stat3) are discussed with respect to the context within which Stat3-mediated effects are elicited within the developing and adult mammalian nervous system. Stat3 signals are pivotal to the proliferation and differentiation of neural stem cells. They also participate in neuronal regeneration and cancers of the nervous system. An analysis of the context in which Stat3 activation occurs in these processes provides a potential predictive paradigm with which novel methods for intervention may be designed.

Cellular responses to Sindbis virus infection of neural progenitors derived from human embryonic stem cells

“…The expression of active phosphorylated (Y705) STAT3 (pSTAT3) was down-regulated by SINV at 24 h.p.i, suggesting a negative regulation of JAK/STAT pathway upon infection. pSTAT3 is required for normal hNPC differentiation, and the reduction in this protein possibly led to impaired differentiation potential [ 25 ]. Expression of Phospho-p44/42 MAPK (pERK1/2) was similarly down-regulated by SINV at 24 h.p.i.…”

“…The JAK/STAT pathway plays a pivotal role in balancing hNPCs lineage specific differentiation [ 25 ]. The reduced pSTAT3 level in SINV-infected hNCPs indicates that the virus probably impaired cell specific differentiation into this cell type.…”

PLZF Regulates Fibroblast Growth Factor Responsiveness and Maintenance of Neural Progenitors

“…Rather, FGFR activation appeared to stimulate the STAT3 pathway. STAT3 forms a prominent node in multiple receptor tyrosine kinase and cytokine signaling pathways, and its activation can result in a wide range of effects including NPC maintenance and gliogenesis [72]. During early CNS development, STAT3 promotes SOX2 expression, and disruption of its activity can impair the emergence of NESTIN + NPCs from embryonic stem cells differentiated in vitro [56].…”

Identification of STAT3 and STAT5 proteins in the rat suprachiasmatic nucleus and the Day/Night difference in astrocytic STAT3 phosphorylation in response to lipopolysaccharide

“…Ligand binding to specific cell‐surface receptors activates tyrosine kinases of the Jak family that phosphorylate STAT proteins. Activated STATs make homo‐ and heterodimers, translocate to the nucleus, and affect gene transcription (Rajan, ). In addition to this classical signaling model, STATs can mediate gene expression even in their unphosphorylated state (Yang and Stark, ; Timofeeva and Tarasova, ), or they can interact with other transcription factors such as SP1 or HSF‐1, with coactivators such as CBP/p300 or with extracellular signal‐related kinase 1/2 (ERK1/2) kinases (Pircher et al, ; Chatterjee‐Kishore et al, ; Wyszomierski and Rosen, ).…”