FUNCTIONAL-ANALYSIS OF PHOSPHORYLATION AT SERINE-532 OF HUMAN C-MYB BY MAP KINASE

The c-myb proto-oncogene encodes a transcription factor that is implic ated in regulatory events during hematopoiesis. It contains negative r egulatory domains at both the amino- and carboxy-termini. Here we desc ribe that human c-Myb can be phosphorylated by mitogen-activated prote in kinases (MAPK's) at serine 532 of the carboxy (C-) terminal regulat ory domain in vitro. This serine residue can also be phosphorylated in vivo upon serum-stimulation of Jurkat cells. Expression of a constitu tively active form of Ras together with c-Myb in transient transfectio n experiments had no effect on the transcriptional activity of c-Myb, while expression of a polypeptide containing the c-Myb C-terminal doma in stimulated c-Myb activity. This effect is reduced upon MAPK-depende nt phosphorylation of serine 532. Our data suggest that the MAPK-depen dent state of phosphorylation modifies the cellular function of c-Myb by modulating its interaction with a putative inhibitory factor.