p190-A RhoGAP Antibody

• 产品编号：CST-2513S      品牌：CST       原厂货号：2513S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

p190-A RhoGAP Antibody检测内源性p190-A RhoGAP (GRLF1)总蛋白。通过人工合成人源p190-A RhoGAP蛋白中间区域相应的多肽片段去免疫动物从而制备出多克隆抗体。通过多肽亲和层析纯化抗体。Rho family small GTPases包括Rho、Rac和cdc42，该家族是不同的生物进程中的关键调节因子例如细胞骨架的构建、细胞生长和分化、转录调控以及细胞粘附/运动(1,2)。这些蛋白质的活性通过GTP的结合被控制，如以GTP结合状态那它们是活性状态，而如以GDP结合状态则它们是失活状态。三种调控性蛋白通过平衡GTP/GDP结合水平控制GTPases的活性：鸟嘌呤核苷酸交换因子(GEFs)通过GDP交换成GTP从而促进活性状态；鸟嘌呤核苷酸分解抑制剂(GDIs)隔绝GDP结合形式并且可能调节它们的细胞内定位；GTPase激活蛋白 (GAPs)增加GTP水解从而促进失活状态。p190 RhoGAP家族由两个相关蛋白p190-A和p190-B组成，它们都广泛表达并且包含有一个氨基端GTPase区域和一个羧基端RhoGAP催化区域。缺少p190-B RhoGAP的小鼠显示大量的Rho激活和在转录因子CREB的激活减少(3)。这些老鼠的表型类似于CREB敲除的老鼠，伴随着细胞体积减少和胸腺和神经发育的缺失(3)。缺失p190-B的细胞也展示脂肪形成的缺陷，认为这条通路对脂肪和肌细胞形成的开关作用是至关重要的 (4)。越来越多的证据显示p190经历酪氨酸磷酸化，这激活它的GAP区域(4-6)。酪氨酸磷酸化的水平通过Src过表达被提高(5,6)。IGF-1处理通过磷酸化和p190-B RhoGAP的激活从而下调Rho，因此IGF信号的提高涉及脂肪形成(4)。p190-A蛋白以作为肿瘤抑制因子为特征，基于在培养的细胞中逆转v-Ha-Ras诱导的恶性肿瘤的能力(7)。染色体区域包括p190-A基因的缺失和重排已经涉及一些人类肿瘤的发展(8)。p190-A蛋白也能结合有丝分裂原诱导转录因子TFII-I，从而在细胞质中的隔绝和抑制它的活性。p190-A蛋白在Tyr308位点的磷酸化 减少了与TFII-I蛋白的吸附，减轻这个抑制作用 (9)。p190-A蛋白也能抑制小鼠中生长因子诱导神经胶质瘤，以及影响培养的细胞中卵裂沟形成和胞质分裂(11)。

1. Peck, J. et al. (2002) FEBS Lett. 528, 27-34.
2. Moon, S.Y. and Zheng, Y. (2003) Trends Cell Biol. 13, 13-22.
3. Wang, Z. et al. (1996) Cell Growth Differ 7, 123-33.
4. Tikoo, A. et al. (2000) Gene 257, 23-31.
5. Jiang, W. et al. (2005) Mol Cell 17, 23-35.
6. Wolf, R.M. et al. (2003) Genes Dev 17, 476-87.
7. Su, L. et al. (2003) J Cell Biol 163, 571-82.
8. Sordella, R. et al. (2002) Dev Cell 2, 553-65.
9. Sordella, R. et al. (2003) Cell 113, 147-58.
10. Chang, J.H. et al. (1995) J Cell Biol 130, 355-68.
11. Roof, R.W. et al. (1998) Mol Cell Biol 18, 7052-63.

原厂资料：

Specificity / Sensitivity

p190-A RhoGAP Antibody detects endogenous levels of total p190-A RhoGAP protein (GRLF1).

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to central residues of human p190-A RhoGAP. Antibodies are purified by peptide affinity chromatography.

Background

The Rho family of small GTPases, including Rho, Rac and Cdc42, are key regulators of diverse biological processes such as cytoskeletal organization, cell growth and differentiation, transcriptional regulation, and cell adhesion/motility (1,2). The activities of these proteins are controlled by GTP binding such that in the GTP-bound state they are active, and in the GDP-bound state they become inactive. Three classes of regulatory proteins control the activity of the GTPases by balancing the levels of GTP/GDP binding: the guanine nucleotide exchange factors (GEFs), which promote the active state by facilitating the exchange of GDP for GTP; the guanine nucleotide dissociation inhibitors (GDIs), which sequester the GDP-bound forms and may regulate their intracellular localization; and the GTPase activating proteins (GAPs), which increase GTP hydrolysis to promote the inactive state. The p190 RhoGAP family consists of two related proteins, p190-A and p190-B, which are both widely expressed and contain an amino-terminal GTPase domain and a carboxy-terminal RhoGAP catalytic domain. Mice lacking p190-B RhoGAP show excessive Rho activation and a reduction in activation of the transcription factor CREB (3). Phenotypes of these mice are similar to those of CREB knockouts, with reduced cell size, as well as defects in thymus and neural development (3). Cells deficient in p190-B also display defective adipogenesis, suggesting this pathway is critical for the "adipogenesis-myogenesis switch." (4). There is increasing evidence that p190 undergoes tyrosine phosphorylation, which activates its GAP domain (4-6). Levels of tyrosine phosphorylation are enhanced by Src overexpression (5,6). IGF-1 treatment downregulates Rho through phosphorylation and activation of p190-B RhoGAP, thereby enhancing IGF signaling implicated in adipogenesis (4).p190-A has been characterized as a tumor suppressor based on its ability to reverse v-Ha-Ras-induced malignancy in cultured cells (7). Loss or rearrangement of the chromosomal region containing the gene for p190-A has been implicated in the development of some human tumors (8). p190-A can also bind the mitogen-inducible transcription factor TFII-I sequestering it in the cytoplasm and inhibiting its activity. Phosphorylation of p190-A at Tyr308 reduces its affinity for TFII-I, relieving the inhibition (9). p190-A can also inhibit growth factor-induced gliomas in mice (10) and affect cleavage furrow formation and cytokinesis in cultured cells (11).

1. Peck, J. et al. (2002) FEBS Lett. 528, 27-34.
2. Moon, S.Y. and Zheng, Y. (2003) Trends Cell Biol. 13, 13-22.
3. Wang, Z. et al. (1996) Cell Growth Differ 7, 123-33.
4. Tikoo, A. et al. (2000) Gene 257, 23-31.
5. Jiang, W. et al. (2005) Mol Cell 17, 23-35.
6. Wolf, R.M. et al. (2003) Genes Dev 17, 476-87.
7. Su, L. et al. (2003) J Cell Biol 163, 571-82.
8. Sordella, R. et al. (2002) Dev Cell 2, 553-65.
9. Sordella, R. et al. (2003) Cell 113, 147-58.
10. Chang, J.H. et al. (1995) J Cell Biol 130, 355-68.
11. Roof, R.W. et al. (1998) Mol Cell Biol 18, 7052-63.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody