 However, testing the relative importance of the genomic and nongenomic mechanisms in vivo has been prevented by the absence of specific molecular mechanisms for the nongenomic effects that could be blocked by mutation of the receptor without disrupting its direct effects on gene expression.A molecular mechanism for non-genomic signaling through the nuclear thyroid hormone receptor TRβ involves the phosphatidylinositol 3-kinase (PI3K).This signaling can be blocked by a single tyrosine to phenylalanine substitution in TRβ without disrupting direct gene regulation.