Novel method for transducing protein-protein interactions

The cell according to any one of the preceding claims, wherein said response regulatory protein comprises a receiver domain fused to an effector domain, wherein said receiver domain is phosphorylatable by said DHp domain of said first or said second variant, and said effector domain is activatable or inhibitable by the phosphorylated receiver domain.

The cell according to any one of the preceding claims, wherein

• said effector domain is a transcriptional activating domain,
• said cell comprises a fourth nucleic acid comprising a gene of interest under control of an inducible promoter recognizable by said transcriptional activating domain,
• wherein upon activation of said transcriptional activating domain the expression of said gene of interest is induced.

The cell according to any one of the preceding claims, wherein

• said first and said second variant are variants of the EnvZ kinase, said response regulatory protein comprises or a is the OmpR response regulatory protein, or
• said first and said second variant are variants of the NarX kinase, said receiver domain comprises or a is the NarL response regulatory protein (SEQ ID 6), and said effector domain is or comprises a VP16 transcriptional activation domain (Vp48, SEQ ID 7).

The cell according to any one of the preceding claims, wherein said first or said second variant is or comprises a variant selected from EnvZ180to450 (SEQ ID 8), EnvZ223to450 (SEQ ID 9), NarX176to598 (SEQ ID 10) and NarX379to598 (SEQ ID 11).

The cell according to any one of the preceding claims, wherein said first nucleic acid sequence and/or said second nucleic acid sequence and/or said third nucleic acid sequence is optimized towards the codon usage of said cell.

The cell according to any one of the preceding claims, wherein said first nucleic acid sequence and/or said second nucleic acid sequence and/or said third nucleic acid sequence is under transcriptional control of a constitutive promoter.

The cell according to any one of the preceding claims, wherein said first variant and said second variant are identical.

The cell according to claim any one of the preceding claims, wherein said histidine kinase belongs to the transphosphorylation family.

The cell according to any one of the preceding claims, wherein

• said first variant comprises a DHp domain that does not comprise a histidine residue accessible by said CA domain of first or said second variant of said histidine kinase, and/or
• said second variant comprises a CA domain that is not able to bind ATP.

The cell according to any one of the preceding claims, wherein

• said first variant is or comprises variant NarX379-598 (H399Q) (SEQ ID NO 12) or NarX176to598 (H399Q), and/or
• said second variant is or comprises variant NarX379-598 (N509A) (SEQ ID NO 13) or NarX176to598 (N509A).

The cell according to any one of the preceding claims, wherein specific binding of said first polypeptide and said second polypeptide is triggerable by a ligand specifically recognizable by said first and/or said second polypeptide.

The cell according to any one of the preceding claims, wherein

• said first polypeptide consists of or comprises a G-protein coupled receptor and said second polypeptide consists of or comprises a cytosolic ligand of said G-protein coupled, particularly beta-arrestin, or
• said first polypeptide consists of or comprises a T cell receptor and said second polypeptide is or comprises ZAP-70.

The cell according to any one of the preceding claims, wherein said cell is a mammalian cell, particularly a human cell.