phosphorylation of the cystic fibrosis transmembrane conductance regulator by cyclic amp - dependent protein kinase is essential for opening the cftr chloride channel . a short segment containing many negatively charged amino acids within the regulatory domain of cftr is a critical regulator of the chloride channel activity . an isolated neg2 polypeptide may be expressed as a separate sequence that stimulates cftr channel openings at lower concentrations , but that inhibits cftr channel openings at higher concentrations . residues in the neg2 sequence were substituted to produce a polypeptide that exerts only an activating effect on cftr . one such polypeptide is the q4n2neg2 polypeptide . exogenous q4n2neg2 exerts stimulatory effects on both wild - type and mutant g551d cftr function , without exhibiting inhibitory activity at any concentration .