Loss of T-cell protein tyrosine phosphatase induces recycling of the platelet-derived growth factor (PDGF) beta-receptor but not the PDGF alpha-receptor.
We have previously shown that the T-cell protein tyrosine phosphatase (TC-PTP) dephosphorylates the platelet-derived growth factor (PDGF) beta-receptor. Here, we show that the increased PDGF beta-receptor phosphorylation in TC-PTP knockout (ko) mouse embryonic fibroblasts (MEFs) occurs primarily on the cell surface. The increased phosphorylation is accompanied by a TC-PTP-dependent, monensin-sensitive delay in clearance of cell surface PDGF beta-receptors and delayed receptor degradation, suggesting PDGF beta-receptor recycling. Recycled receptors could also be directly detected on the cell surface of TC-PTP ko MEFs. The effect of TC-PTP depletion was specific for the PDGF beta-receptor, because PDGF alpha-receptor homodimers were cleared from the cell surface at the same rate in TC-PTP ko MEFs as in wild-type MEFs. Interestingly, PDGF alphabeta-receptor heterodimers were recycling. Analysis by confocal microscopy revealed that, in TC-PTP ko MEFs, activated PDGF beta-receptors colocalized with Rab4a, a marker for rapid recycling. In accordance with this, transient expression of a dominant-negative Rab4a construct increased the rate of clearance of cell surface receptors on TC-PTP ko MEFs. Thus, loss of TC-PTP specifically redirects the PDGF beta-receptor toward rapid recycling, which is the first evidence of differential trafficking of PDGF receptor family members.
Karlsson
Susann
S
Ludwig Institute for Cancer Research, Uppsala University Biomedical Center, S-751 24 Uppsala, Sweden.
Kowanetz
Katarzyna
K
Sandin
Asa
A
Persson
Camilla
C
Ostman
Arne
A
Heldin
Carl-Henrik
CH
Hellberg
Carina
C
D000818:Animals; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism
D008024:Ligands; D011993:Recombinant Fusion Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases; C516653:Ptpn2 protein, mouse; D020695:rab4 GTP-Binding Proteins