Department of Cell Morphology and Molecular Neurobiology, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Universitaetsstr. 150, 44780 Bochum, Germany.
Exp Brain Res. 2009 Sep;198(1):37-47. doi: 10.1007/s00221-009-1932-0. Epub 2009 Jul 29.
The regulation of protein phosphorylation plays an essential role in virtually all aspects of eukaryotic development. Beginning with the regulation of the cell cycle to cellular proliferation and differentiation, the delicate balance between the phosphorylating activity of kinases and the dephosphorylation by phosphatases controls the outcome of many signal transduction cascades. The generation of cellular diversity occurs in an environment that is structured by the extracellular matrix (ECM) which forms a surrounding niche for stem and progenitor cells. Cell-cell and cell-matrix interactions elicit specific signaling pathways that control cellular behavior. In pathological situations such as neural degenerating diseases, gene expression patterns and finally the composition of the ECM change dramatically. This leads to changes of cell behavior and finally results in the failure of regeneration and functional restoration in the adult central nervous system. In order to study the roles of tyrosine phosphatases and ECM in this context, we analyzed the effects of laser-induced retinal injury on the regulation of the receptor protein tyrosine phosphatases (RPTP) RPTPBr7, Phogrin and RPTPbeta/zeta. The latter occurs in several isoforms, including the soluble released chondroitin sulfate proteoglycan phosphacan that is expressed in the developing retina. The receptor variants RPTPbeta/zeta(long) and RPTPbeta/zeta(short) may serve as receptors of tenascin-proteins and serve as modulators of cell intrinsic signaling in response to the ECM. Using quantitative real-time RT-PCR analysis, we show here a time-dependent pattern of gene expression of these molecules following laser lesions of the retina.
蛋白质磷酸化的调节在真核生物发育的几乎所有方面都起着至关重要的作用。从细胞周期的调节到细胞增殖和分化，激酶的磷酸化活性和磷酸酶的去磷酸化之间的微妙平衡控制着许多信号转导级联的结果。细胞多样性的产生发生在由细胞外基质（ECM）形成的环境中，它为干细胞和祖细胞形成周围小生境。细胞-细胞和细胞-基质相互作用引发特定的信号通路，控制细胞行为。在神经退行性疾病等病理情况下，基因表达模式最终导致 ECM 的组成发生巨大变化。这导致细胞行为的改变，最终导致成年中枢神经系统再生和功能恢复的失败。为了研究酪氨酸磷酸酶和 ECM 在这种情况下的作用，我们分析了激光诱导的视网膜损伤对受体蛋白酪氨酸磷酸酶（RPTP）RPTPBr7、Phogrin 和 RPTPbeta/zeta 调节的影响。后者存在几种同工型，包括在发育中的视网膜中表达的可溶性释放的软骨素硫酸盐蛋白聚糖神经磷蛋白。受体变体 RPTPbeta/zeta(long) 和 RPTPbeta/zeta(short)可能作为 tenascin 蛋白的受体，并作为细胞内固有信号对 ECM 反应的调节剂。通过定量实时 RT-PCR 分析，我们在这里显示了这些分子在视网膜激光损伤后随时间表达的时间依赖性模式。
