ERK5 is activated

Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase family. ERK5 is twice the size of the ERK1/2, containing a conserved amino terminal kinase domain that is 53% identical to ERK1/2, and a unique carboxyterminal region which contains potential binding sites for signalling molecules such as CRK, PI3 kinase and SRC. The second proline-rich region may interact with actin, targeting the kinase to a specific location in the cell. In contrast to ERK1 and ERK2, which are activated by neurotrophins (NTs), cAMP, and neuronal activity in neurons, ERK5 appears to be activated only by neurotrophins. The small GTPase Rap1 and the MEKK2 or MEKK3 kinases are critical upstream signaling molecules mediating neurotrophin stimulation of ERK5 in neurons. MEKK2 or MEKK3 activate MEK5, which appears to be localised in intracellular vesicles. MEK5 then activates ERK5. Once phosphorylated, ERK5 translocates to the nucleus.

细胞外信号调节激酶5（ERK5）是丝裂原活化蛋白激酶家族的成员。ERK5的体积是ERK1/2的两倍，包含一个保守的氨基末端激酶结构域，其与ERK1/2的序列同源性达到53%，以及一个独特的羧基末端区域，该区域含有潜在的结合位点，可结合信号分子如CRK、PI3激酶和SRC。第二个脯氨酸富集区域可能与肌动蛋白相互作用，将激酶定位于细胞内的特定位置。与ERK1和ERK2不同，它们在神经元中由神经营养因子（NTs）、cAMP和神经元活动激活，ERK5似乎仅由神经营养因子激活。小GTP酶Rap1以及MEKK2或MEKK3激酶是关键的上游信号分子，介导神经营养因子对神经元中ERK5的刺激。MEKK2或MEKK3激活MEK5，MEK5似乎定位于细胞内小泡中。随后，MEK5激活ERK5。一旦磷酸化，ERK5将转移至细胞核。