However, in other tissues, such as liver and adipose, activation of the UPR is thought maladaptive; in the prevailing view, IRE1 mediated activation of the Jun-N terminal kinase 1 (JNK1, also known as mitogen activated protein kinase-8, MAPK8) leads to serine phosphorylation of insulin receptor substrate-1 at a key serine (307) which is thought to lead to impaired insulin signaling (Ozcan et al.,