抗原激活 B 细胞受体（BCR），导致第二信使的产生
中文名称
通路描述
成熟 B 细胞表达 IgM 和 IgD 免疫球蛋白，与 Ig-alpha (CD79A, MB-1) 和 Ig-beta (CD79B, B29) 结合形成 B 细胞受体 (BCR)。抗原与免疫球蛋白结合后，通过 Src 家族酪氨酸激酶（包括 LYN、FYN 和 BLK）磷酸化 Ig-alpha 和 Ig-beta 胞质尾部的免疫受体酪氨酸基激活基序 (ITAMs)。蛋白激酶 SYK 也可参与 ITAMs 的磷酸化。活化的 SYK 及其他激酶磷酸化 BLNK (SLP-65, BASH)、BCAP 和 CD19。磷酸化的 BLNK、BCAP 和 CD19 作为支架招募效应分子至细胞膜并组装成信号复合物。BCAP 和 CD19 招募磷脂酰肌醇 3-激酶 (PI3K)。BLNK 招募磷脂酶 C gamma (主要在 B 细胞中为 PLC-gamma2)、NCK、BAM32、BTK、VAV1 和 SHC。效应分子由 SYK 和其他激酶磷酸化。磷酸化的 BCAP 招募 PI3K，该酶通过 SYK 依赖性机制被磷酸化，产生磷脂酰肌醇 -3,4,5-三磷酸 (PIP3)。磷酸化的 CD19 同样招募 PI3K。PIP3 通过 PH 域招募并激活 PLC-gamma1 和 PLC-gamma2。BTK 通过其 SH2 域结合磷酸化的 BLNK。BTK 磷酸化 PLC-gamma2，激活磷脂酶活性。磷酸化的 BLNK 招募 PLC-gamma、VAV、GRB2 和 NCK。PLC-gamma 水解磷脂酰肌醇 -4,5-二磷酸产生肌醇 -1,4,5-三磷酸 (IP3) 和二酰甘油 (DAG)。IP3 结合内质网上的受体，导致内质网中的 Ca2+ 离子释放到细胞质中。内质网中钙离子的耗竭反过来激活 STIM1 与 ORAI 和 TRPC1 通道（以及可能的其他 TRP 通道）结合，导致细胞外钙离子流入。
英文描述
Formation of definitive endoderm The endoderm in mammalian embryos originates from two different populations of cells: the visceral endoderm, which is present before gastrulation as the hypoblast underlying the epiblast, and the definitive endoderm, which is derived from epiblast cells ingressing through the anterior-most region of the primitive streak. After ingression, the cells of the definitive endoderm then intercalate with the cells of the visceral endoderm to form the embryonic endoderm that will give rise to the gut and visceral organs associated with the gut such as the pancreas and liver (reviewed in Lewis and Tam 2006, Nowotschin et al. 2019). In the discoid human gastrula (differs from the rodent gastrula which acquires a cup shape), the endoderm initially is organized in a flat epithelial sheet that later rolls into a tube to form the gut. Due to ethical considerations, research on gastrulation is undertaken primarily in non-human primate species (for example Bergmann et al. 2022) and stem cells (D'Amour et al. 2005, reviewed in Salehin et al. 2022), which have provided insight into germ layer formation in human embryos.
The definitive endoderm originates in the anterior region of the primitive streak where there are high levels of NODAL signaling (inferred from mouse embryos in Vincent et al. 2003) and lower levels of BMP signaling (inferred from mouse embryos in Bachiller et al. 2000) and Wnt signaling (inferred from mouse embryos in Mukhopadhyay et al. 2001). In mouse, Eomesodermin (EOMES), whose expression is activated by NODAL signaling via SMAD2 and SMAD3 in the primitive streak, is required for formation of both mesoderm and endoderm (Arnold et al. 2008). Experiments in human embryonic stem cells and mouse embryos indicate that EOMES is a core element of a gene regulatory network that specifies definitive endoderm by activating expression of transcription factors such as FOXA2 and SOX17 which then activate sets of endodermally expressed genes (Teo et al. 2011, Chia et al. 2019). As endoderm progenitors enter the primitive streak they redistribute E-cadherin (CDH1) on their surface, which may play a role in sorting the cells into an epithelial layer (inferred from mouse homologs in Viotti et al. 2014). Unlike mesoderm, endoderm progenitors do not undergo a complete epithelial to mesenchymal transition (EMT) (inferred from mouse embryos and stem cells in Scheibner et al. 2021). They do not switch cadherin expression from E-cadherin (CDH1) to N-cadherin (CDH2) and do not require the EMT transcription factor SNAI1 (inferred from mouse homologs in Scheibner et al. 2021). The endodermal transcription factor FOXA2 may repress EMT activity (inferred from the mouse homolog in Scheibner et al. 2021).
Though no single marker gene is expressed exclusively in definitive endoderm, the definitive endoderm is characterized by the expression of a combination of genes, including FOXA2, SOX17, GATA4, GATA6, CXCR4, GSC, and E-cadherin (CDH1). CDH1, a general marker of epithelial cells, and the chemokine receptor CXCR4 are often used together as surface markers of definitive endoderm (inferred from mouse homologs in Yasunaga et al. 2005).
The definitive endoderm originates in the anterior region of the primitive streak where there are high levels of NODAL signaling (inferred from mouse embryos in Vincent et al. 2003) and lower levels of BMP signaling (inferred from mouse embryos in Bachiller et al. 2000) and Wnt signaling (inferred from mouse embryos in Mukhopadhyay et al. 2001). In mouse, Eomesodermin (EOMES), whose expression is activated by NODAL signaling via SMAD2 and SMAD3 in the primitive streak, is required for formation of both mesoderm and endoderm (Arnold et al. 2008). Experiments in human embryonic stem cells and mouse embryos indicate that EOMES is a core element of a gene regulatory network that specifies definitive endoderm by activating expression of transcription factors such as FOXA2 and SOX17 which then activate sets of endodermally expressed genes (Teo et al. 2011, Chia et al. 2019). As endoderm progenitors enter the primitive streak they redistribute E-cadherin (CDH1) on their surface, which may play a role in sorting the cells into an epithelial layer (inferred from mouse homologs in Viotti et al. 2014). Unlike mesoderm, endoderm progenitors do not undergo a complete epithelial to mesenchymal transition (EMT) (inferred from mouse embryos and stem cells in Scheibner et al. 2021). They do not switch cadherin expression from E-cadherin (CDH1) to N-cadherin (CDH2) and do not require the EMT transcription factor SNAI1 (inferred from mouse homologs in Scheibner et al. 2021). The endodermal transcription factor FOXA2 may repress EMT activity (inferred from the mouse homolog in Scheibner et al. 2021).
Though no single marker gene is expressed exclusively in definitive endoderm, the definitive endoderm is characterized by the expression of a combination of genes, including FOXA2, SOX17, GATA4, GATA6, CXCR4, GSC, and E-cadherin (CDH1). CDH1, a general marker of epithelial cells, and the chemokine receptor CXCR4 are often used together as surface markers of definitive endoderm (inferred from mouse homologs in Yasunaga et al. 2005).
所含基因
15 个基因