MAPK8 and Insulin resistance: However, as a Ser/Thr kinase, it is likely that JNK1 phosphorylates multiple sites on IRS1/2, since subsequent studies found that a serine to alanine mutation on residue 307 (S307A mutation) on IRS1, a mutation that prevents phosphorylation by JNK1, does not protect mice from HFD-induced insulin resistance [82], and that only with multiple serine mutations into alanine at position 302, 307 and 612 was insulin sensitivity restored in skeletal muscle [83].