title: Proline-serine-threonine phosphatase interacting protein 1 inhibition of T-cell receptor signaling depends on its SH3 domain.
abstract: Proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) is an adaptor protein associated with the cytoskeleton that is mainly expressed in hematopoietic cells. Mutations in PSTPIP1 cause the rare autoinflammatory disease called pyogenic arthritis, pyoderma gangrenosum, and acne. We carried out this study to further our knowledge on PSTPIP1 function in T cells, particularly in relation to the phosphatase lymphoid phosphatase (LYP), which is involved in several autoimmune diseases. LYP-PSTPIP1 binding occurs through the C-terminal homology domain of LYP and the F-BAR domain of PSTPIP1. PSTPIP1 inhibits T-cell activation upon T-cell receptor (TCR) and CD28 engagement, regardless of CD2 costimulation. This function of PSTPIP1 depends on the presence of an intact SH3 domain rather than on the F-BAR domain, indicating that ligands of the F-BAR domain, such as the PEST phosphatases LYP and PTP-PEST, are not critical for its negative regulatory role in TCR signaling. Additionally, PSTPIP1 mutations that cause the pyogenic arthritis, pyoderma gangrenosum and acne syndrome do not affect PSTPIP1 function in T-cell activation through the TCR.
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), CSIC-Universidad de Valladolid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Marcos
authors.forename: Virginia
authors.initials: V
authors.lastname: Ruiz-Martín
authors.forename: María Luisa
authors.initials: ML
authors.lastname: de la Puerta
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Trinidad
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Rodríguez
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: de la Fuente
authors.forename: Mariano
authors.initials: M
authors.lastname: Sánchez Crespo
authors.forename: Andrés
authors.initials: A
authors.lastname: Alonso
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Bayón
mesh_terms: D000152:Acne Vulgaris / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D001170:Arthritis, Infectious / Q000235:genetics*; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000502:physiology; D017511:Pyoderma Gangrenosum / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000502:physiology; D018909:src Homology Domains / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D017252:CD3 Complex; D003598:Cytoskeletal Proteins; C486382:PSTPIP1 protein, human; D011948:Receptors, Antigen, T-Cell; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: PTPN22; T-cell receptor; T cell; proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1); pyogenic arthritis, pyoderma gangrenosum and acne (PAPA)