Tyrosine phosphatases SHP-1 and SHP-2 are associated with distinct tyrosine-phosphorylated proteins.
SHP-1 and SHP-2 are two SH2 domain-containing tyrosine phosphatases. They share significant overall sequence identity but their functions are often opposite. The mechanism underlying this is not well understood. In this study, we have investigated the association of SHP-1 and SHP-2 with tyrosine-phosphorylated proteins in mouse tissues and in cultured cells treated with a potent tyrosine phosphatase inhibitor, pervanadate. Pervanadate was introduced into mice by intravenous injection. It induced robust tyrosine phosphorylation of cellular proteins in a variety of tissues. Both SHP-1 and SHP-2 were phosphorylated on tyrosyl residues upon pervanadate treatment, and they became associated with distinct tyrosine-phosphorylated proteins in different tissues and cells. Among these proteins, PZR and PECAM were identified as major SHP-2-binding proteins while LAIR-1 was shown to be a major SHP-1-binding protein. A number of other proteins are to be identified. We believe that the different binding proteins may determine the distinct physiological functions of SHP-1 and SHP-2. The present study also provides a general method to induce tyrosine phosphorylation of cellular proteins and to study protein-protein interactions involving tyrosine phosphorylation in vivo and in vitro.
Xu
Fengping
F
Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6305, USA.
Xu
Ming-jiang
MJ
Zhao
Runxiang
R
Guerrah
Abdelmadjid
A
Zeng
Fenghua
F
Zhao
Zhizhuang Joe
ZJ
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D010766:Phosphorylation; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D014443:Tyrosine; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C076715:pervanadate; D014638:Vanadates; D014443:Tyrosine; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C516727:Ptpn11 protein, rat; C509248:Ptpn6 protein, mouse; C509250:Ptpn6 protein, rat; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases