Mutation of C-terminal tyrosine residues Y497/Y504 of the Src-family member Bsk/Iyk decreases NIH3T3 cell proliferation

作者：Oberg Welsh C; Anneren C; Welsh M^*

来源：Growth Factors, 1998, 16(2): 111-124.

• tyrosine kinase
• Bsk/Iyk
• cell growth rate
• mutation

To elucidate the properties of the Src-family member Bsk/Iyk, NIH3T3 cells were transfected with wild-type Bsk/Iyk or Bsk/Iyk carrying Y497F, Y504F or Y497/504F mutations. These positions are putatively homologous to tyr-527 in Src, The Bsk/Iyk(Y497/504F) cells displayed a decreased cell growth rate, parallelled by an augmentation of the fraction of cells in G1-phase, The Bsk/Iyk(Y497/504F) double-mutation decreased the [H-3]thymidine incorporation. No effects on NIH3T3 cell growth could be seen in cells expressing wild-type Bsk/Iyk or the other Bsk/Iyk mutants, In vitro kinase reactions performed on immunoprecipitates from NIH3T3 cells expressing wild-type or mutated Bsk/Iyk revealed increased relative [P-32]-incorporation into Bsk/Iyk isoforms containing the Y504F and Y497/504F mutations compared with wild-type Bsk/Iyk, The Y497F and Y497/504F mutations elevated the proportion. of [P-32]-incorporation into a 57 kDa Bsk/Iyk product relative to that into the 60 kDa isoform, The Y497F Bsk/Iyk mutant not only increased the relative amount of p57 Bsk/Iyk but also transferred this isoform to the nuclear subcellular fraction. The results suggest that Bsk/Iyk has unique regulatory properties, and that this kinase might serve a role in inhibiting cell replication.

• 出版日期1998