NCAM 信号传导促进轴突生长
中文名称
通路描述
神经细胞粘附分子 NCAM 是免疫球蛋白（Ig）超家族的一员，并参与许多对神经系统形成和维持至关重要的细胞过程。NCAM 在神经分化和社会性可塑性中的作用被认为取决于细胞内信号转导级联的调节。基于 NCAM 的信号复合物可以通过至少两种机制启动下游细胞内信号：（1）激活 FGFR 和（2）通过与胞质相互作用伙伴如 Fyn 和 FAK 的直接相互作用形成细胞内信号复合物。酪氨酸激酶 Fyn 和 FAK 与 NCAM 结合并发生磷酸化，这暂时激活 MAPK、ERK 1 和 2、cAMP 反应元件结合蛋白（CREB）和转录因子 ELK 和 NFkB。CREB 激活转录那些对神经元轴突生长、生存和社会性可塑性至关重要的基因。NCAM1 介导的细胞内信号转导在下图中有所表示。NCAM1 中的 Ig 域用橙色椭圆表示，Fn 域用绿色方块表示。易被磷酸化的酪氨酸残基用红色圆圈表示，并编号了它们的位置。磷酸化由红色箭头表示，脱磷酸化由黄色表示。Ig，免疫球蛋白结构域；Fn，纤连蛋白结构域；Fyn，原癌基因酪氨酸蛋白激酶 Fyn；FAK，粘附蛋白激酶；RPTPα，受体酪氨酸蛋白磷酸酶；Grb2，生长因子受体结合蛋白 2；SOS，Son of sevenless 同源物；Raf，RAF 原癌基因丝氨酸/苏氨酸蛋白激酶；MEK，MAPK 和 ERK 激酶；ERK，细胞外信号调节激酶；MSK1，细胞因子和应激激活蛋白激酶 1；CREB，环腺苷酸反应元件结合蛋白；CRE，环腺苷酸反应元件。
英文描述
NCAM signaling for neurite out-growth The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons.
NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements.
NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements.
所含基因
17 个基因