JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1

C-Jun NH2 terminal kinases (JNKs) are an evolutionarily conserved family of serine/threonine protein kinases, that belong to mitogen activated protein kinase family (MAPKs - also known as stress-activated protein kinases, SAPKs). The JNK pathway is activated by heat shock, or inflammatory cytokines, or UV radiation. <p>The JNKs are encoded by at least three genes: JNK1/SAPK-gamma, JNK2/SAPK-alpha and JNK3/ SAPK-beta. The first two are ubiquitously expressed, whereas the JNK3 protein is found mainly in brain and to a lesser extent in heart and testes. As a result of alternative gene splicing all cells express distinct active forms of JNK from 46 to 55 kDa in size. Sequence alignment of these different products shows homologies of >80%. In spite of this similarity, the multiple JNK isoforms differ in their ability to bind and phosphorylate different target proteins, thus leading to the distinctive cellular processes: induction of apoptosis, or enhancment of cell survival, or proliferation.<p>Activation of JNKs is mediated by activated TAK1 which phosphorylates two dual specificity enzymes MKK4 (MAPK kinase 4) and MKK7(MAPK kinase 7).

C-Jun氨基末端激酶（JNKs）是一类进化上保守的丝氨酸/苏氨酸蛋白激酶家族，隶属于丝裂原活化蛋白激酶家族（MAPKs，亦称应激活化蛋白激酶，SAPKs）。JNK通路可通过热休克、炎症细胞因子或紫外线辐射而激活。JNKs由至少三个基因编码：JNK1/SAPK-γ、JNK2/SAPK-α和JNK3/SAPK-β。前两者在全身广泛表达，而JNK3蛋白主要存在于大脑，在心脏和睾丸中含量较低。由于选择性剪接，所有细胞均表达从46至55 kDa大小的不同活性JNK形式。这些不同产物的序列比对显示同源性超过80%。尽管存在这种相似性，多种JNK同种异构体在结合和磷酸化不同靶蛋白的能力上存在差异，从而导致了不同的细胞过程：凋亡诱导、细胞存活增强或增殖。<p>JNKs的激活由激活的TAK1介导，TAK1磷酸化两种双特异性酶MKK4（MAPK激酶4）和MKK7（MAPK激酶7）。