COMPARATIVE-STUDY OF 3 PROTEIN-TYROSINE PHOSPHATASES - CHICKEN PROTEIN-TYROSINE-PHOSPHATASE-LAMBDA DEPHOSPHORYLATES C-SRC TYROSINE-527

To examine the substrate preference of protein tyrosine phosphatases ( PTPs), we compared the activity of three transmembrane PTPs on dephosp horylation and regulation of c-Src and v-Src: chicken PTP lambda (ChPT P lambda), chicken PTP alpha (ChPTP alpha), and human leukocyte common antigen-related molecule (HLAR). In vitro, all three PTPs dephosphory lated v-Src, but only ChPTP lambda dephosphorylated c Src. Their activ ities were also compared in Cos cells coexpressing Src and the phospha tase domains of three PTPs. These domains were fused with peptides for myristylation, so they associated with the cellular membrane. When c- Src was coexpressed with myrPTP lambda, its kinase activity was elevat ed 3-4-folds. This activation was less obvious when c-Src was coexpres sed with myrPTP alpha or myrLAR. Analysis by cyanogen bromide cleavage showed that ChPTP lambda and myrPTP lambda dephosphorylated Tyr-527 o f c-Src. Our data demonstrated the different activities of three PTPs on phosphoproteins, suggesting that Src Tyr-527 may require more speci fic PTP(s) than Src Tyr-416 for dephosphorylation in vivo.