title: N-terminal sequences direct the autophosphorylation states of the FER tyrosine kinases in vivo.
abstract: p94(fer) and p51(ferT) are two tyrosine kinases which share identical SH2 and kinase domains but differ in their N-terminal regions. While p94(fer) is expressed in most mammalian cells, the accumulation of p51(ferT) is restricted to meiotic spermatocytes. Here we show that the different N-terminal tails of p94(fer) and p51(ferT) 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 p94(fer). Moreover, the ectopically expressed N-terminal tail of p94(fer) could act as a dominant negative mutant and associated with the endogenous p94(fer) protein in CHO cells. This increased significantly the percentage of cells residing in the G0/G1 phase, thus suggesting a role for p94(fer) in the regulation of G1 progression. Unlike p94(fer), overexpressed p51(ferT) was not autophosphorylated in COS1 cells. However, removal of the unique N-terminal 43 aa of p51(ferT) or the replacement of this region by a parallel segment from p94(fer) endowed the modified p51(ferT) with the ability to autophosphorylate. The unique N-terminal sequences of p51(ferT) thus interfere with its ability to autophosphorylate in vivo. These experiments indicate that the N-terminal sequences of the FER tyrosine kinases direct their different cellular autophosphorylation states, thereby dictating their different cellular functions.
authors.affiliation: Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Orlovsky
authors.forename: I
authors.initials: I
authors.lastname: Ben-Dor
authors.forename: S
authors.initials: S
authors.lastname: Priel-Halachmi
authors.forename: H
authors.initials: H
authors.lastname: Malovany
authors.forename: U
authors.initials: U
authors.lastname: Nir
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000201:enzymology; D019556:COS Cells; D006224:Cricetinae; D016193:G1 Phase / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017433:Protein Structure, Secondary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D014162:Transfection
chemical_list: D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases