TI - Negative control of the Myc protein by the stress-responsive kinase Pak2 . AB - Pak2 is a serine/threonine kinase that participates in the cellular response to stress . Among the potential substrates for Pak2 is the protein Myc , encoded by the proto - oncogene MYC . Here we demonstrate that Pak2 phosphorylates Myc at three sites ( T358 , S373 , and T400 ) and affects Myc functions both in vitro and in vivo . Phosphorylation at all three residues reduces the binding of Myc to DNA , either by blocking the requisite dimerization with Max ( through phosphorylation at S373 and T400 ) or by interfering directly with binding to DNA ( through phosphorylation at T358 ) . Phosphorylation by Pak2 inhibits the ability of Myc to activate transcription , to sustain cellular proliferation , to transform NIH 3T3 cells in culture , and to elicit apoptosis on serum withdrawal . These results indicate that Pak2 is a negative regulator of Myc , suggest that inhibition of Myc plays a role in the cellular response to stress , and raise the possibility that Pak2 may be the product of a tumor suppressor gene .