Table 1.
Protein tyrosine phosphatases (PTPs) in T-cell activation
| PTP | Gene name | Role in T-cell activation |
|---|---|---|
| CD45 | PTPRC | Positively regulates TCR signalling by dephosphorylation of inhibitory site of LCK and FYN |
| CD148 | PTPRJ | Positively regulates TCR signalling by dephosphorylation of inhibitory site of LCK; may also negatively regulate TCR signalling by dephosphorylation of LAT and PLCγ1 |
| RPTPα | PTPRA | Positively regulates TCR signalling by dephosphorylation of inhibitory site of LCK and FYN |
| RPTPκ | PTPRK | Needed for development of CD4+ T cells; mechanism unclear |
| LAR | PTPRF | Negatively regulates TCR signalling in thymocytes by dephosphorylation of LCK and FYN |
| LYP/Pep | PTPN22 | Negatively regulates TCR signalling by dephosphorylation of inhibitory site of LCK, FYN, ZAP-70 and others; binds CSK |
| PTP-PEST | PTPN12 | Negatively regulates TCR signalling by dephosphorylation of Cas, Pyk2, FAK, paxilin; binds CSK |
| SHP-1 | PTPN6 | Negatively regulates T-cell activation through ITIM/ITSM receptors, cytokine receptors, dephosphorylates LCK, ZAP-70 and others |
| SHP-2 | PTPN11 | Positively regulates T-cell activation by increasing ERK activation; binds Gab2; may also inhibit T-cell activation through ITIM/ITSM receptors |
| TCPTP | PTPN2 | Negatively regulates T-cell activation by inhibiting IL-2 production |
| PTPH1 | PTPN3 | Inhibits TCR signalling when over-expressed by dephosphorylating immunoreceptor tyrosine-based activation motifs; dephosphorylates valosin-containing protein and interacts with TACE |
| PTP-MEG1 | PTPN4 | Inhibits T-cell activation when over-expressed |
| PTP-BAS | PTPN13 | Inhibits apoptosis by binding CD95/FAS; regulates cytokine secretion by inhibiting STAT proteins |
| PTP-MEG2 | PTPN9 | Promotes secretion – necessary for secretory vesicle formation |
| HePTP | PTPN7 | Negatively regulates TCR signalling by dephosphorylation of ERK and p38 |
| MKP-1 | DUSP1 | Negatively regulates T-cell activation by dephosphorylation of MAPKs in nucleus |
| PAC-1 | DUSP2 | Negatively regulates T-cell activation by dephosphorylation of p38 and ERK in nucleus |
| MKP-2 | DUSP4 | Negatively regulates IL-2 signalling and proliferation of CD4+ T cells through regulation of STAT5 phosphorylation |
| MKP-3 | DUSP6 | Negatively regulates T-cell activation by dephosphorylation of ERK in cytosol; may mediate TLR4-induced inhibition of TCR signalling |
| MKP-5 | DUSP10 | Negatively regulates T-cell activation by dephosphorylation of JNK in cytosol and nucleus |
| MKP-7 | DUSP16 | Regulates the balance between Th1/Th2 cells through dephosphorylation of JNK in cytosol |
| VHR | DUSP3 | Dephosphorylates p38, ERK and STAT5; promotes cell-cycle progression |
| PTEN | PTEN | Opposes PI3K activity by dephosphorylating PIP3; functions as tumour suppressor |
| LMPTP | ACP1 | Positively regulates signalling by dephosphorylation of inhibitory site of ZAP-70; may prevent TCR clustering by inhibiting cytoskeletal rearrangement through FAK |
ERK, extracellular signal-regulated kinase; IL-2, interleukin-2; ITIM/ITSM, immunoreceptor tyrosine-based inhibitory motifs/immunoreceptor tyrosine-based switch motifs; JNK, Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; STAT5, signal transducer and activator of transcription; TCR, T-cell receptor; Th1, T helper type 1; TLR4, Toll-like receptor 4.