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干貨 | p38 MAPK Related作為對外界物理和化學(xué)性質(zhì)變化的響應(yīng)，哺乳動物細(xì)胞激活有絲分裂原激活蛋白激酶 (MAPK) 的四個特征性亞家族：ERK1/2、JNK、p38 和 ERK5。其中 p38 MAPKs 是一類保守的絲氨酸-蘇氨酸蛋白激酶，可被多種細(xì)胞外炎癥因子 (如TNF-α, IL-1)，細(xì)菌脂多糖 LPS，趨化因子以及紫外線等多種應(yīng)激刺激激活。激活后的 p38 MAPK 通過調(diào)控下游多種酶及轉(zhuǎn)錄因子表達(dá)活性，從而對細(xì)胞功能進(jìn)行調(diào)節(jié)。大量研究表明，p38 MAPK 活性對正常免疫和炎癥反應(yīng)至關(guān)重要。同時，在腫瘤發(fā)生以及缺血再灌注損傷中也起著重要作用。 MAPK經(jīng)典激活途徑 與 p38 MAPK 相關(guān)靶點(diǎn) MAPK 經(jīng)典激活途徑是通過 MAPK 激酶激酶 (MAP3K)-MAPK 激酶 (MAP2K) 途徑實(shí)現(xiàn)的。首先 MAP3K 被激活, 隨后，激活的 MAP3K 能磷酸化并激活MAP2K，接下來，MAP2K 磷酸化 MAPK，使MAPK激活。當(dāng)然，也存在與 MAP3K -MAP2K 無關(guān)的，非典型的自磷酸化激活途徑。在p38 MAPK激活途徑 (即其上游信號通路) 中，屬于MAP3K 類如 MEKK1-4，Tpl2，MLKs，ASK1/2，DLK，TAK1，TAO1/2；屬于MAP2K 類如 MKK3 和 MKK6 (有時是 MKK4，可激活 p38α)。
p38 MAPK 包含四種亞型，分別為 p38α (MAPK 14)，p38β (MAPK 11)，p38γ (MAPK 12)，p38δ (MAPK 13)。它們具有不同的組織表達(dá)模式，p38α 在大多數(shù)細(xì)胞類型中以顯著水平普遍表達(dá)，而其他 p38 亞型似乎以更具組織特異性的方式表達(dá)，如 p38β 在腦中表達(dá)較為豐富，p38γ 是在骨骼肌中，而 p38δ 則是在內(nèi)分泌腺中。p38 MAPK 激活后，由其介導(dǎo)的下游磷酸化調(diào)節(jié)主要為兩大類蛋白，一類為轉(zhuǎn)錄因子，如 p53，ATF2，Elk1，MEF2 和 C/EBPβ，另一類為蛋白激酶，包括 MK2 (也稱為 MAPKAP2)，MSK1，MNK1 和 MNK2。
如何選擇 p38 MAPK抑制劑 ? p38 MAPK 的經(jīng)典抑制劑 SB 203580 (RWJ 64809)
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