p38激酶在癌症研究中的进展（磷酸化抗体免费送）

转自：北京义翘神州

MAPK（丝裂原活化蛋白激酶）通路参与调控与癌症发展相关的一系列细胞行为，包括增殖、分化、凋亡、炎症和免疫等。异常的MAPK信号传导可能导致细胞增殖过度或失控，以及对细胞凋亡的抵抗。ERK、JNK和p38是在致癌中发挥作用的三大MAPK。

p38 MARK家族包括四个亚型：p38α（MAPK14）、p38β（MAPK11）、p38γ（MAPK12）和p38δ（MAPK13），整体序列同源性>60%，激酶域内的同源性>90%。激酶结构域中部存在保守序列TGY，其中180位苏氨酸Thr（p38γ为183位）及182位酪氨酸Tyr（p38γ为185位）可被MKK3/4、TAK1等磷酸化。

p38在多种组织中以不同的表达水平普遍表达。p38α在几乎所有类型细胞中表达，而p38β主要在脑组织中表达，p38γ主要在骨骼肌中表达，p38δ主要在肾等组织中表达。p38 MAPK最初被确定为一种磷酸化不同转录因子的蛋白激酶。p38通路的失调，与癌症的发展、转移、自噬和肿瘤微环境等密切相关。

p38在不同组织的表达（源自参考文献：doi: 10.1038/s41417-023-00622-1）

在癌症的不同阶段或不同癌症中，p38扮演不同的角色。如在结直肠肿瘤发生早期，p38α在正常结肠上皮细胞中维持肠道稳态和屏障功能，抑制结肠炎相关肿瘤的发生。另一方面，在肿瘤进展期，p38α通过促进转化上皮细胞的增殖和抑制细胞凋亡来促进结肠肿瘤的发展。p38在肿瘤微环境中也发挥双重作用，如在乳腺癌中，肿瘤源性的GM-CSF激活p38，诱导骨髓细胞ARG1表达并抑制T细胞的抗肿瘤功能。另一方面，AMPK激活p38，导致Treg中的PD-1表达并抑制肿瘤进展。这种多变的表现可能是由于p38能够调控大量不同底物（p38的底物超过两百种），不同信号通路之间又存在着复杂的crosstalk。

p38在肿瘤进程中的双面性（源自参考文献：doi:10.3390/ijms21061913）

p38磷酸化抗体验证数据

Recombinant Phospho-p38 MAPK (Thr180, Tyr182) Antibody, Rabbit Monoclonal， Cat: 110435-R0004

 WB应用：多肽竞争特异性验证

Western blot analysis of extracts from serum-starved NIH-3T3, untreated (line A); treated with UV (30 min), without peptide (line B) or antigen-specific phosphopeptide (line C) or antigen-specific peptide (line D) using Phospho-p38 MAPK (Thr180, Tyr182) rabbit monoclonal Antibody at 1:1000 dilution.

 IHC应用：磷酸酶特异性验证

Immunohistochemical analysis of paraffin-embedded human carcinoma of sigmoid tissue,untreated (left) or lambda phosphatase-treated (right), using Recombinant Phospho-p38 MAPK (Thr180-Tyr182) Antibody, Rabbit Monoclonal at 1:500 dilution.

 IF应用：磷酸酶特异性验证

Immunofluorescence staining of Phospho-p38 MAPK (Thr180, Tyr182) in serum-starved NIH-3T3 cells, untreated (left), treated with UV (30mins) (middle) or treated with UV (30mins) and lambda phosphatase (right). Cells were fixed with 4% PFA, permeabilzed with 0.1% Triton X-100 in PBS, blocked with 10% serum, and incubated with rabbit anti-Mouse Phospho-p38 MAPK (Thr180, Tyr182) monoclonal antibody (dilution ratio 1:60) at 4℃ overnight. Then cells were stained with the Alexa Fluor®488-conjugated Goat Anti-rabbit IgG secondary antibody (green). Positive staining was mainly localized to Nucleus.

 抗体稳定性测试：加速实验

Recombinant Phospho-p38 MAPK (Thr180, Tyr182) Antibody, Rabbit Monoclonal was placed in 25℃ for 8 days, in 25℃ for 16 days, in 37℃ for 3.5 days, in 37℃ for 7 days respectively. The cell lysates were serum-starved NIH-3T3, untreated or treated with UV (30 min). The antibody after accelerated by different temperature still showed significant specificity.

【参考文献】

1. García-Hernández, et al. The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer. Int J Mol Sci, 2021. https://doi.org/10.3390/ijms23010370

2. Martínez-Limón, et al. The p38 Pathway: From Biology to Cancer Therapy. Int J Mol Sci, 2020. https://doi.org/10.3390/ijms21061913

3. Thuy Phan, et al. P38 kinase in gastrointestinal cancers. Cancer Gene Therapy (2023)

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