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. In order to identify nuclear substrates of Abl, we constructed a constitutively active and nuclear form of the protein. We found that active nuclear Abl efficiently phosphorylate c‐Jun, a transcription factor not previously known 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 nuclear tyrosine phosphorylation and represents a reversal of previously known signalling models.

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