The homeodomain of Nkx2.2 carries two cooperatively acting nuclear localization signals.
NK-2 family members of homeodomain proteins have been identified as important regulators of growth and development in the ventral forebrain, heart, lung, and thyroid. In addition, Nk2.2 expression has been detected in the pancreas, where it is vital for the final differentiation of beta-cells. In our present paper, we have analyzed the domains necessary for nuclear transport of Nkx2.2. With the help of deletion mutants we identified two separate nuclear localization signals (NLS). Interestingly, both NLSs are situated in the homeodomain. They belong to the monopartite class of NLS; the proximal NLS has the sequence KKRKRR and lies at the very N-terminus of the homeodomain, while the more distal NLS RYKMKRAR is at the homeodomain C-terminus. Each NLS per se is sufficient for nuclear transport of Nkx2.2 into the nucleus, although inefficiently. Both identified NLSs act cooperatively in mediating complete nuclear transport of Nkx2.2.
Hessabi
B
B
Department of Biochemistry, Medical School, Ernst-Moritz-Arndt-University, Greifswald, Germany. hessabi@mail.uni-greifswald.de
Schmidt
I
I
Walther
R
R
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D016384:Consensus Sequence; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection; D029961:Zebrafish Proteins
D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish; C084010:pancreatic and duodenal homeobox 1 protein