Abstract: Methods and compositions useful for protein tyrosine phosphatases (PTPs) are disclosed. Peptides are provided which, in one aspect, are useful as substrates for the determination of PTP activity. In contrast to the current approaches, such peptides provide a general substrate for which variations in PTP enzymatic activity due to the assay are minimized. The present invention also discloses methods for determining the presence or amount of PTP. Because of the increased sensitivity of the methods, PTPs can be detected in situations where only limiting amounts of sample, e.g., tissue extracts or immunoprecipitates, are available.