Compositions and methods for monitoring the phosphorylation of natural binding partners

A method for monitoring activity of an enzyme comprising contacting at least one of an isolated natural binding domain and a binding partner therefor with said enzyme, wherein neither said natural binding domain nor said binding partner therefor comprises an anti-phosphotyrosine monoclonal antibody, contacting said isolated natural binding domain and said binding partner therefor and performing a detection step to detect association or dissociation of said isolated natural binding domain and said binding partner therefor as a result of contacting one or both of said isolated natural binding domain and said binding partner with said enzyme, wherein said isolated natural binding domain includes a site for post-translational phosphorylation and binds said binding partner in a manner dependent upon phosphorylation or dephosphorylation of said site and wherein at least one of said isolated natural binding domain and said binding partner is labeled with a detectable label wherein detection of binding of said isolated natural binding domain and said binding partner as a result of said contacting is indicative of enzyme activity.