Calmodulin regulates the translocation of Grb7 into the nucleus

We describe in this report the presence of a nuclear localization signal (NLS) overlapping the calmodulin-binding domain (CaM-BD) of the growth factor receptor bound protein 7 (Grb7). We show that deletion of the CaM-BD of Grb7 prevents its nuclear localization, and that its Src homology 2 (SH2) domain might participate as well in the translocation process. Also, treating cells with the CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) enhances the presence of Grb7 in the nucleus. We propose that CaM inhibits the translocation of Grb7 to the nucleus after binding to its CaM-BD and therefore occluding its overlapping NLS.

► Grb7 binds calmodulin (CaM).
► Deletion of the CaM-binding domain (CaM-BD) of Grb7 prevents nuclear entry.
► Inhibition of CaM facilitates Grb7 entry into the nucleus.
► The SH2 domain of Grb7 participates in the translocation process.
► CaM controls Grb7 nuclear translocation.