JNK Biochemistry

JNK is one of the three branches of MAPK superfamily of serine/threonine protein kinases. Other members of this superfamily are p38 kinases and the ERKs (Kyriakis and Avruch, 2012). In mammals, there are 3 JNK genes: Jnk1, Jnk2, and Jnk3 on 3 different chromosomes, and each mammalian JNK gene has alternative splicing forms (Derijard et al., 1994). JNK is involved in many physiological and pathological processes. The JNK pathway plays a major role in apoptosis. JNK pathway is required for neuronal cell death induced by many apoptotic stimuli such as DNA damage, oxidative stress, α-amyloid exposure, low potassium, excitotoxic stress, 6-OHDA, UV irradiation, nerve growth factor (NGF) deprivation, trophic support withdrawal and tumor necrosis factor …show more content…
It is also known as protein kinase B (PKB). It contains at least three subunits (AKT1/PKBa, AKT2/PKBb and AKT3/PKBg) in humans (Song et al., 2005; Fayard et al., 2010). Researches have shown that AKT executes numerous tasks through phosphorylation of several cellular substrates and plays an important role in physiological and pathological settings. The phosphorylation of PKB Ser473 is reduced in both the cytosolic and membrane fractions of PD midbrain (Timmons et al., 2009). PKB and its phosphorylation at Ser473 is also consistently reduced in the dopaminergic neurons of the substantia nigra with loss of these neurons and hence are consequently reduced in PD. Another study has confirmed reduced phosphorylation of PKB at both Thr308 and Ser473 in substantia nigra dopaminergic neurons in PD patients (Malagelada et al., 2008). It suggests that reduced phosphorylation of PKB is restricted to dopaminergic neurons as non-neuromelanin containing neurons of the midbrain expressed similar levels of PKB and phosphorylated PKB in both control and PD