Differential activities of protein tyrosine phosphatases in intact cells.
We have employed transient co-overexpression of protein tyrosine phosphatases (PTPs) with a panel of receptor tyrosine kinases (RTKs) to investigate molecular parameters that regulate dephosphorylation activity and specificity in intact cells. Our results demonstrate clear differences in susceptibility of various forms of different RTKs to the action of PTP 1B, T-cell phosphatase (TC-PTP), and CD45, which suggests cellular compartmentalization as a major factor defining activity and overall function. TC-M PTP, a nonlocalized cytosolic mutant, is deregulated and is therefore able to efficiently suppress v-erbB- and v-fms-induced cell transformation, which is not observed with the intact TC-PTP or PTP 1B. The transmembrane PTP CD45 displays more selectivity but appears to be already active during transport to the cell surface. Dephosphorylation activity is also dependent on relative RTK/PTP expression levels and can be modulated by the SH2 domain-containing noncatalytic subunit of phosphatidylinositol 3'-kinase, p85. Overexpression of high affinity binding proteins could therefore contribute to RTK-induced cell transformation and cancer.
Lammers
R
R
Department of Molecular Biology, Max-Planck-Institut für Biochemie, Martinsried, Germany.
Bossenmaier
B
B
Cool
D E
DE
Tonks
N K
NK
Schlessinger
J
J
Fischer
E H
EH
Ullrich
A
A
D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D007668:Kidney; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D008715:Methionine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020794:Receptor Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases