PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jbcThe Journal of Biological Chemistry
 
J Biol Chem. 2015 June 26; 290(26): 15948.
PMCID: PMC4481199

The PTP1B Phosphatase Demonstrates Exquisite Specificity♦

Protein-tyrosine Phosphatase and Kinase Specificity in Regulation of SRC and Breast Tumor Kinase

♦ See referenced article, J. Biol. Chem. 2015, 290, 15934–15947

Phosphatases, like kinases, work specifically. In this Paper of the Week, a team led by Nicholas K. Tonks at Cold Spring Harbor Laboratory and W. Todd Miller at Stony Brook University countered the notion that phosphatases are nondiscriminatory in their mode of action. They demonstrated that the protein tyrosine phosphatase PTP1B displays substrate specificity by analyzing its effects on two kinases, BRK and SRC. The two kinases are structurally similar and functionally related; both are regulated by inhibitory and activating sites of tyrosine phosphorylation. The investigators showed that PTP1B inhibited BRK, an oncogene known to be involved in breast cancer, when it dephosphorylated a key tyrosine within BRK's catalytic domain. In the case of SRC, PTP1B indirectly enhanced the activity of the kinase by antagonizing the action of the kinase CSK that inhibits SRC's activity. The authors concluded that their findings showed that the combined effects of tyrosine kinases and phosphatases “may be integrated to regulate signaling, with both classes of enzymes displaying exquisite specificity.”

An external file that holds a picture, illustration, etc.
Object name is zbc0261521250001.jpg

Model to illustrate the regulation of BRK and SRC. A, PTP1B played a negative role in controlling BRK activation by directly dephosphorylating the autophosphorylation site of the kinase. B, by dephosphorylating PAG at Tyr-317 to exclude CSK-mediated SRC inactivation, PTP1B indirectly sustained and potentiated the activity of SRC.


Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology