A nuclear tyrosine phosphorylation circuit: c-Jun as an activator and substrate of c-Abl and JNK

The nuclear function of the c-Abl tyrosine kinase is not well understood. I n order to identify nuclear substrates of Abl, we constructed a constitutiv ely active and nuclear form of the protein, We found that active nuclear Ab l efficiently phosphorylate c-Jun, a transcription factor not previously kn own to be tyrosine phosphorylated, After phosphorylation of c-Jun by Abl on Tyr170, both proteins interacted via the SH2 domain of Abl, Surprisingly, elevated levels of c-Jun activated nuclear Abl, resulting in activation of the JNK serine/threonine kinase, This phosphorylation circuit generates nuc lear tyrosine phosphorylation and represents a reversal of previously known signalling models.