Fcgamma receptor-mediated inhibition of human B cell activation : the role of SHP-2 phosphatase
Co-clustering of the type II receptors binding the Fc part of IgG (FcgammaRIIb) and B cell receptors results in the translocation of cytosolic, negative regulatory molecules to the phosphorylated immunoreceptor tyrosine-based inhibitory motif (P-ITIM) of the FcgammaRIIb. SH2 domain-containing protein tyrosine phosphatases (SHP-1 and SHP-2), and the polyphosphoinositol 5'-phosphatase (SHIP) have been reported earlier to bind to murine FcgammaRIIb P-ITIM. However, neither the functional substrates of these enzymes, nor the mechanism of the inhibition are fully resolved. We show here that the human FcgammaRIIb binds SHP-2 when co-clustered with the B cell receptors, whereas its synthetic P-ITIM peptide bindes SHP-2 and SHIP in lysates of the Burkitt's lymphoma cell line BL41. The P-ITIM peptide binding enhances SHP-2 activity, resulting in dephosphorylation and release of P-ITIM-bound SHIP and Shc. Moreover, P-ITIM-bound SHP-2 dephosphorylates synthetic peptides corresponding to the sites of tyrosine phosphorylation on SHIP and Shc, indicating that these proteins are its potential substrates. Thus SHP-2-induced dephosphorylation may modulate the intracellular localization and/or activity of SHIP and Shc, thereby inhibiting further activation pathways which they mediate.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
1999 |
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| Erschienen: |
1999 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
European journal of immunology - 29(1999), 6 vom: 19. Juni, Seite 1980-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Koncz, G [VerfasserIn] |
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| Anmerkungen: |
Date Completed 08.07.1999 Date Revised 24.04.2018 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM103147993 |
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| 100 | 1 | |a Koncz, G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Fcgamma receptor-mediated inhibition of human B cell activation |b the role of SHP-2 phosphatase |
| 264 | 1 | |c 1999 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 08.07.1999 | ||
| 500 | |a Date Revised 24.04.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Co-clustering of the type II receptors binding the Fc part of IgG (FcgammaRIIb) and B cell receptors results in the translocation of cytosolic, negative regulatory molecules to the phosphorylated immunoreceptor tyrosine-based inhibitory motif (P-ITIM) of the FcgammaRIIb. SH2 domain-containing protein tyrosine phosphatases (SHP-1 and SHP-2), and the polyphosphoinositol 5'-phosphatase (SHIP) have been reported earlier to bind to murine FcgammaRIIb P-ITIM. However, neither the functional substrates of these enzymes, nor the mechanism of the inhibition are fully resolved. We show here that the human FcgammaRIIb binds SHP-2 when co-clustered with the B cell receptors, whereas its synthetic P-ITIM peptide bindes SHP-2 and SHIP in lysates of the Burkitt's lymphoma cell line BL41. The P-ITIM peptide binding enhances SHP-2 activity, resulting in dephosphorylation and release of P-ITIM-bound SHIP and Shc. Moreover, P-ITIM-bound SHP-2 dephosphorylates synthetic peptides corresponding to the sites of tyrosine phosphorylation on SHIP and Shc, indicating that these proteins are its potential substrates. Thus SHP-2-induced dephosphorylation may modulate the intracellular localization and/or activity of SHIP and Shc, thereby inhibiting further activation pathways which they mediate | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Receptors, IgG |2 NLM | |
| 650 | 7 | |a Tyrosine |2 NLM | |
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| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
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| 650 | 7 | |a PTPN6 protein, human |2 NLM | |
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| 650 | 7 | |a Protein Tyrosine Phosphatase, Non-Receptor Type 11 |2 NLM | |
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| 650 | 7 | |a Protein Tyrosine Phosphatase, Non-Receptor Type 6 |2 NLM | |
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| 650 | 7 | |a Ptpn11 protein, mouse |2 NLM | |
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| 650 | 7 | |a Ptpn6 protein, mouse |2 NLM | |
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| 650 | 7 | |a EC 3.1.3.48 |2 NLM | |
| 700 | 1 | |a Pecht, I |e verfasserin |4 aut | |
| 700 | 1 | |a Gergely, J |e verfasserin |4 aut | |
| 700 | 1 | |a Sármay, G |e verfasserin |4 aut | |
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