Phospho-Insulin Receptor (Tyr999)抗体特异性结合抗原：抗体本身不能直接溶解或杀伤带有特异抗原的靶细胞，通常需要补体或吞噬细胞等共同发挥效应以**病原微生物或导致病理损伤。然而，抗体可通过与病毒或**的特异性结合，直接发挥中和病毒的作用。
产品编号xy- 16680R
英文名称Phospho-Insulin Receptor (Tyr999)
中文名称磷酸化胰岛素受体抗体
别 名Insulin Receptor (phospho Y999); p-Insulin Receptor (phospho Y999); CD 220; CD220; CD220 antigen; HHF 5; HHF5; human insulin receptor; INSR; INSR_HUMAN; Insulin receptor subunit beta; IR 1; IR; IR-1; IR1.
说 明 书100ul
产品类型磷酸化抗体
研究领域细胞生物 信号转导 生长因子和** 激酶和磷酸酶 糖尿病 新陈代谢 细胞膜蛋白
抗体来源Rabbit
克隆类型Polyclonal
Phospho-Insulin Receptor (Tyr999)抗体交叉反应 Human, Rat, Chicken, Cow, Horse,
产品应用WB=1:500-2000 ELISA=1:500-1000 IHC-P=1:400-800 IHC-F=1:400-800 Flow-Cyt=1μg/Test ICC=1:100-500 IF=1:100-500 （石蜡切片需做抗原修复）
not yet tested in other applications.
optimal dilutions/concentrations should be determined by the end user.
分 子 量70kDa
细胞定位细胞膜
性 状Lyophilized or Liquid
浓 度1mg/1ml
免 疫 原KLH conjugated synthesised phosphopeptide derived from human Insulin Receptor around the phosphorylation site of Tyr999:PE(p-Y)LS
亚 型IgG
纯化方法affinity purified by Protein A
储 存 液0.01M TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol.
Phospho-Insulin Receptor (Tyr999)抗体保存条件Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C.
PubMedPubMed
产品介绍background:
After removal of the precursor signal peptide, the insulin receptor precursor is post-translationally cleaved into two chains (alpha and beta) that are covalently linked. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Function:
Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
Subunit:
Tetramer of 2 alpha and 2 beta chains linked by disulfide bonds. The alpha chains contribute to the formation of the ligand-binding domain, while the beta chains carry the kinase domain. Forms a hybrid receptor with IGF1R, the hybrid is a tetramer consisting of 1 alpha chain and 1 beta chain of INSR and 1 alpha chain and 1 beta chain of IGF1R. Interacts with SORBS1 but dissociates from it following insulin stimulation. Binds SH2B2. Activated form of INSR interacts (via Tyr-999) with the PTB/PID domains of IRS1 and SHC1. The sequences surrounding the phosphorylated NPXY motif contribute differentially to either IRS1 or SHC1 recognition. Interacts (via tyrosines in the C-terminus) with IRS2 (via PTB domain and 591-786 AA); the 591-786 would be the primary anchor of IRS2 to INSR while the PTB domain would have a stabilizing action on the interaction with INSR. Interacts with the SH2 domains of the 85 kDa regulatory subunit of PI3K (PIK3R1) in vitro, when autophosphorylated on tyrosine residues. Interacts with SOCS7. Interacts (via the phosphorylated Tyr-999), with SOCS3. Interacts (via the phosphorylated Tyr-1185, Tyr-1189, Tyr-1190) with SOCS1. Interacts with CAV2 (tyrosine-phosphorylated form); the interaction is increased with 'Tyr-27'phosphorylation of CAV2 (By similarity). Interacts with ARRB2 (By similarity). Interacts with GRB10; this interaction blocks the association between IRS1/IRS2 and INSR, significantly reduces insulin-stimulated tyrosine phosphorylation of IRS1 and IRS2 and thus decreases insulin signaling. Interacts with GRB7 (By similarity). Interacts with PDPK1. Interacts (via Tyr-1190) with GRB14 (via BPS domain); this interaction protects the tyrosines in the activation loop from dephosphorylation, but promotes dephosphorylation of Tyr-999, this results in decreased interaction with, and phosphorylation of, IRS1. Interacts (via subunit alpha) with ENPP1 (via 485-599 AA); this interaction blocks autophosphorylation. Interacts with PTPRE; this interaction is dependent of Tyr-1185, Tyr-1189 and Tyr-1190 of the INSR. Interacts with STAT5B (via SH2 domain). Interacts with PTPRF.
Subcellular Location:
Cell membrane.
Tissue Specificity:
Isoform Long and isoform Short are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform Short is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.
Post-translational modifications:
After being transported from the endoplasmic reticulum to the Golgi apparatus, the single glycosylated precursor is further glycosylated and then cleaved, followed by its transport to the plasma membrane.
DISEASE:
Rabson-Mendenhall syndrome Leprechaunism Diabetes mellitus, non-insulin-dependent Familial hyperinsulinemic hypoglycemia 5 Insulin-resistant diabetes mellitus with acanthosis nigricans type A.
Similarity:
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Insulin receptor subfamily.
Contains 3 fibronectin type-III domains.
Contains 1 protein kinase domain.
Gene ID:
3643
Phospho-Insulin Receptor (Tyr999)抗体（antibody,
Ab）是由效应B细胞（效应**B细胞）分泌，机体用于抵御外来物质，如病毒，**等抗原，结构呈“Y”字型的球状蛋白质，仅仅存在于脊椎动物的血液和B**细胞膜表面。凡是能够跟抗体结合的物质，均被称作抗原，因此对于抗抗体（能够结合抗体的抗体）来说，抗体本身也是一种抗原物质。
Phospho-Insulin Receptor (Tyr999)抗体普通抗体重链和轻链的结构
重链结构：普通的**球蛋白具有2条重链（H链），分子量约为50kD,有μ、δ、γ、ε和α五种重链亚型，对应的**球蛋白名称分别为IgM、IgG、IgA、IgD和IgE。
轻链结构： 普通**球蛋白具有2条轻链（L链），分子质量约25kDa，有κ链和λ链两种亚型，这两种轻链决定了Ig的亚型类别（IgG1，IgG2，IgG3，IgG4）。一个天然的Ig分子两条轻链总是相同的，但在同一个体内可存在分别带有κ或λ链的抗体分子。不同种属生物体内两型轻链的比例不同，正常人血清**球蛋白κ链：λ链约为2：1，而在小鼠的比例为20：1。
2.2抗体Fab段和Fc段
IgG经木瓜蛋白酶酶切后裂解为2个完全相同的Fab段和1个Fc段,每个Fab段都为单价,可与抗原结合但不会再发生凝集反应；经胃蛋白酶酶切后裂解为1个完整F(ab)2片段和碎片化的Fc片段,F(ab’)2片段为双价,可同时结合两个抗原表位。Fab段为抗原结合片段（fragment of antigen binding，Fab），相当于抗体分子的两个臂，由一个完整的轻链和重链的VH和CH1结构域组成。Fc段为可结晶段（fragment crystallizable，Fc）相当于Ig的CH2和CH3结构域，是Ig与效应分子或者细胞相互作用的部位。Fab段包含完整的可变区，以及恒定区的CH1区域。Fc段仅指Ig恒定区CH2和CH3的区域，相当于Y字结构下面那一部分。
合格 IBRDC1 环指蛋白217抗体
合格 IBTK Bruton酪氨酸激酶抑制剂蛋白抗体
合格 合格 Bcl-2 alpha Bcl2 alpha蛋白抗体
合格 Aquaporin 5 水通道蛋白5抗体
合格 IFI44L 干扰素诱导蛋白44样蛋白抗体
合格 合格 IFIT1 干扰素诱导的三角形四肽重复蛋白1抗体
合格 IFIT1B 干扰素诱导的三角形四肽重复蛋白1B抗体
合格 IFRD2 干扰素相关发育调节因子2抗体
合格 IFT172 细胞纤毛内转运同源蛋白172抗体
合格 合格 Profilin 1 前纤维蛋白1抗体
合格 IGFL2 胰岛素生长因子样家族成员2抗体
合格 IGFL4 胰岛素生长因子样家族成员4抗体
合格 IGSF9B **球蛋白超家族成员B抗体
合格 合格 CK19 细胞角蛋白19抗体
合格 Elastase 3B 胰腺弹性蛋白酶3B抗体
合格 Elastase-2B 胰腺弹性蛋白酶2B抗体
合格 GLP-1R 胰高血糖素样肽-1受体/GLP-1受体抗体
合格 Reelin 络丝蛋白抗体
合格 Annexin IV 膜粘连蛋白 A4抗体
合格 ENPP3 ENPP3蛋白抗体
合格 APOH 载脂蛋白H抗体
合格 合格 F-Actin 纤维状肌动蛋白抗体
合格 BBC3/PUMA p53正向细胞凋亡调控因子抗体
合格 CSMD1 CSMD1抗体
合格 FANCF 范可尼贫血相关蛋白F抗体
合格 Rab27a Rab27a蛋白抗体
合格 factor XIII 凝血因子13抗体(纤维蛋白稳定因子)
合格 CK20 细胞角蛋白20抗体
合格 CA I 碳酸酐酶1抗体
合格 OL 嗅球蛋白2抗体