Tyrosine phosphorylation of the TATA element modulatory factor by the FER nuclear tyrosine kinases

Abstract The FER locus in the mouse encodes two tyrosine kinases, p94 fer and p51 ferT . While p94 fer accumulates in the cytoplasm and nucleus of most mammalian cells the expression of p51 ferT is restricted to the nucleus of meiotic primary spermatocytes. The cellular function of the FER kinases is not understood, nor has a substrate for these enzymes been characterized. To identify putative substrates of p94 fer and p51 ferT , the two enzymes were used as `baits' in the yeast two-hybrid screening system. cDNAs encoding the mouse TATA element modulatory factor (TMF) were repeatedly isolated in this assay. TMF was previously shown to bind the TATA element in RNA polymerase II promoters and impaired their functioning in a cell free transcription system. Both p94 fer and p51 ferT phosphorylated the TMF protein in in vitro and in vivo kinase assays. Sequential deletions showed that the carboxy-terminal region of TMF was essential for phosphorylation. In situ hybridization analysis revealed the preferential accumulation of TMF transcripts in meiotic spermatogenic and oogenic cells. p94 fer and p51 ferT may thus modulate the suppressive activity of TMF during cellular growth and in defined differentiation processes.