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心血管相关——VEGF信号通路

发布时间:2023-02-23 04:08:00

血管的形成

 

血管生成:胚胎早期成血管细胞分化形成原始血管

血管新生:即从已经存在的血管中构建出来新的血管,正常情况下血管新生仅发生在胚胎发育期,创伤愈合期和女性的生理周期,病理条件下也会出现异常的血管新生。

血管内皮生长因子(VEGF)是成人中健康和疾病期间血管发育和血液及淋巴管功能的主要调节因子。VEGF由几种细胞类型如成纤维细胞,炎性细胞和许多肿瘤细胞产生,通常响应于通过HIF-1a途径增加的肿瘤缺氧。目前,VEGF家族由五个结构相关因子组成:VEGFA(也称为VEGFA165,并且研究最为充分),VEGFB,VEGFC,VEGFD和胎盘生长因子(PlGF)。VEGF家族成员主要以同型二聚体多肽形式存在,尽管天然异二聚体的VEGFA和PlGF也已经被报到。内皮细胞上的主要VEGF受体是VEGFR2。VEGFR2对于发育期间和成人,生理学和病理学中的内皮细胞生物学研究是重要的靶标。目前关于VEGF受体的研究还是以VEGFR2信号传导较多。

VEGF信号通路

 

1.丝裂原活化的蛋白激酶(MAPK)途径

VEGF结合到VEGFR2上,引起SHC磷酸化,活化的SHC与接头蛋白(GRB2)结合,GRB2通过SH2结构域结合鸟苷酸交换蛋白(SOS),使之接近Ras,然后进一步激活PAPK级联反应:Raf1→MEK1/2→ERK1/2。VEGF可诱导P38-MARK活化,P38-MAPK继而活化MAPKAKP-2/3,并使丝状肌动蛋白(F-Actin)聚合调节分子和热休克蛋白27(HSP27)发生磷酸化,引起肌动蛋白骨架的重组,产生EC移行。

2.PI3K-Akt/PKB途径

VEGF与VEGFR2结合后,PI3K发生磷酸化,活化的PI3K与底物PIP2结合将其转化为PIP3,PIP3诱导Akt/PKB磷酸化。磷酸化的Akt既可通过磷酸化BAD和Caspase9(天冬氨酸特异性半胱氨酸蛋白酶)抑制BAD和Caspase9的活性,诱导EC增生和移行,也可通过激活eNOS产生NO,控制造血功能和AMI(急性骨髓白血病)细胞的生长。

3.Ca2+ —磷脂依赖性激酶途径

VEGF活化PLCγ水解膜组分PIP2产生IP3和DAG。IP3诱导细胞内Ca2+释放,促进前列腺素的生成,提高血管渗透性。Ca2+使PKC结合并聚合至质膜,在DAG(二酯甘油)的作用下活化,PKC也可作为eNOS和Raf1-MEK1/2-ERK1/2的上游激活物,促进NO的产生,促进基因的表达和细胞的增殖。

靶标 产品货号 产品名称 反应种属 应用
BAD db915 Bad Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db11004 Bad Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db21725 Phospho-Bad (Ser112) Rabbit pAb Human,Mouse,Rat WB,IP
CASP9 db6217 Caspase-9 (1D1) Mouse mAb Human WB
CDC42 db14118 CDC42 Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db4231 CDC42 Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db22154 Phospho-RAC1/Cdc42 (Ser71) Rabbit pAb Human WB
COX2 db14667 COX2 Recombinant Rabbit mAb Mouse WB,ICC/IF,FC,IP
db13375 COX2 Recombinant Rabbit mAb Human,Mouse WB,IHC
db8534 COX2 Rabbit pAb Mouse WB,ICC/IF,FC,IP
db9805 COX2 Rabbit pAb Human,Mouse WB,IHC
db3633 COX2 Rabbit pAb Human,Mouse WB,IHC,IP
db2995 COX2/Cyclooxygenase 2 Rabbit pAb Human,Mouse WB,ICC/IF,FC
ERK  db14725 ERK1 Recombinant Rabbit mAb Human,Mouse WB,IHC,ICC/IF,FC,IP
db4966 ERK1 Rabbit pAb Human,Mouse WB,IHC,ICC/IF,FC,IP
db6569 ERK1 (1D10) Mouse mAb Human,Mouse,Rat IHC-P
db6567 ERK1 (7E7) Mouse mAb Human,Mouse,Rat IHC-P
db6568 ERK1 (8G6) Mouse mAb Human,Mouse,Rat IHC-P
FAK db14504 FAK Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF,FC
db13741 Phospho-FAK (Tyr576) Recombinant Rabbit mAb Human,Mouse,Rat WB,FC
db4203 FAK Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db20970 FAK Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,FC
db11806 FAK Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db2584 Phospho-FAK (Tyr397) Rabbit pAb Human,Mouse,Rat WB,ICC/IF
db12142 Phospho-FAK (Tyr397) Recombinant Rabbit mAb Human,Mouse,Rat WB,ICC/IF
db22202 Phospho-FAK (Tyr576) Rabbit pAb Human,Mouse,Rat WB,FC
db21022 Phospho-FAK (Tyr576/Tyr577) Rabbit pAb Human,Mouse WB,ICC/IF,FC,IP
db6186 FAK (3D8) Mouse mAb Human WB,ICC/IF,IP
MEK1 db20562 MEK1 Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db626 MEK1 Rabbit pAb Human WB,ICC/IF,FC,IP
db1784 MEK1 Rabbit pAb Human WB,IHC,ICC/IF,IP
db13983 MEK1 Recombinant Rabbit mAb Human WB,IHC,ICC/IF,IP
db2079 Phospho-MEK1 (Ser298) Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF
db11915 Phospho-MEK1 (Ser298) Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF
db251 Phospho-MEK1 (Thr286) Rabbit pAb Human WB,IP
db1747 Phospho-MEK1 (Thr292) Rabbit pAb Human WB
db11129 Phospho-MEK1 (Thr292) Recombinant Rabbit mAb Human WB
p38 db14381 p38 Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF
db13080 p38 Recombinant Rabbit mAb Human,Mouse,Rat WB,ICC/IF,FC,IP
db14139 Phospho-p38 (Thr180) Recombinant Rabbit mAb Human WB,FC
db6168 p38 (5A1) Mouse mAb Human,Mouse,Rat,Monkey WB
db6586 p38 (6F5) Mouse mAb Human,Mouse,Rat IHC-P
db20336 p38 Rabbit pAb Human,Mouse,Rat WB,ICC/IF,FC,IP
db387 p38 Rabbit pAb Human,Mouse,Rat WB,ICC/IF,FC,IP,ChIP
db3666 p38 Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF
db5672 Phospho-p38 (Thr180) Rabbit pAb Human WB,FC
db18 Phospho-p38 (Thr180/Tyr182) Rabbit pAb Human,Mouse WB
Paxillin db14728 Paxillin Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF,IP
db12478 Paxillin Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db20547 Paxillin Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,FC,IP
db1638 Paxillin Rabbit pAb Human,Mouse,Rat WB,IHC,ICC/IF,IP
db3855 Phospho-Paxillin (Tyr118) Rabbit pAb Human,Mouse,Rat WB
PI3K db14641 PI3K-gamma Recombinant Rabbit mAb Human WB,FC,IP
db8287 PI3K-gamma Rabbit pAb Human WB,FC,IP
RAF1 db12651 Raf1 Recombinant Rabbit mAb Human WB,IHC,ICC/IF
db2779 Phospho-Raf1 (Ser259) Rabbit pAb Human,Mouse,Rat WB,IHC
db12158 Phospho-Raf1 (Ser259) Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC
db4640 Raf1 Rabbit pAb Human WB,IHC,ICC/IF
SRC db4576 Src Rabbit pAb Human,Mouse,Rat WB
db7312 Src Rabbit pAb Human,Mouse,Rat WB,IHC,FC
db14390 Phospho-Src (Tyr530) Recombinant Rabbit mAb Human,Mouse,Rat WB,ICC/IF,IP
db14294 Src Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,FC
db957 Phospho-Src (Tyr419) Rabbit pAb Human,Mouse,Rat WB,FC
db11012 Phospho-Src (Tyr419) Recombinant Rabbit mAb Human,Mouse,Rat WB,FC
db20533 Phospho-Src (Tyr530) Rabbit pAb Human,Mouse,Rat WB,ICC/IF,IP
VEGF db30174 VEGF Recombinant Rabbit mAb Human IHC,WB
db9395 VEGF Receptor 1 Rabbit pAb Human,Mouse,Rat WB,IHC,IP
db11269 VEGF Receptor 1 Recombinant Rabbit mAb Human,Mouse,Rat WB,IHC,IP
db4606 VEGF Receptor 2 Rabbit pAb Mouse,Rat WB
db8930 VEGF Receptor 2 Rabbit pAb Mouse ICC/IF,FC
db1738 VEGF Receptor 2 Rabbit pAb Human WB,IP
db5907 VEGF Receptor 3 Rabbit pAb Human WB
db5798 VEGF Receptor 3 Rabbit pAb Human FC