N-terminal sequences direct the autophosphorylation states of the FER tyrosine kinases in vivo.

p94fer and p51ferT are two tyrosine kinases which share identical SH2 and kinase domains but differ in their N-terminal regions. While p94fer is expressed in most mammalian cells, the accumulation of p51ferT is restricted to meiotic spermatocytes. Here we show that the different N-terminal tails of p94fer and p51ferT direct different autophosphorylation states of these two kinases in vivo. N-terminal coiled-coil domains cooperated to drive the oligomerization and autophosphorylation in trans of p94fer. Moreover, the ectopically expressed N-terminal tail of p94fer could act as a dominant negative mutant and associated with the endogenous p94fer protein in CHO cells. This increased significantly the percentage of cells residing in the G0/G1 phase, thus suggesting a role for p94fer in the regulation of G1 progression. Unlike p94fer, overexpressed p51ferT was not autophosphorylated in COS1 cells. However, removal of the unique N-terminal 43 aa of p51ferT or the replacement of this region by a parallel segment...