Disease relevance of WIPF1

• Our previous studies have shown that N-WASP is required for the actin-based motility of vaccinia virus and is recruited via Nck and WIP [1].
• We have now identified and characterized the N-WASP WH1 binding motif in WIP in vitro and in vivo using Shigella and vaccinia systems [2].
• Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich Syndrome [3].
• National guidelines for the prevention of hospital infections in The Netherlands were established by the Working Group on Infection Prevention (WIP) in 1981 [4].

Psychiatry related information on WIPF1

• Conditional uncertainty analysis and implications for decision making: the case of WIPP [5].

High impact information on WIPF1

• These results suggest that WIP is important for immunologic synapse formation and T cell activation [6].
• WIP deficiency reveals a differential role for WIP and the actin cytoskeleton in T and B cell activation [6].
• In contrast, WIP-deficient B lymphocytes have enhanced proliferation and CD69 expression following B cell receptor ligation and mount normal antibody responses to T-independent antigens [6].
• WIP stabilizes actin filaments and is important for filopodium formation [6].
• In this review, the authors discuss the possible role of WASP/NWASP and of the newly described protein WIP, which interacts with WASP and NWASP, in coupling signals from the T-cell receptor to the actin-based cytoskeleton [7].

Biological context of WIPF1

• The human WASP-interacting protein, WIP, activates the cell polarity pathway in yeast [8].
• RESULTS: A yeast two-hybrid screen revealed the interaction of the cortactin Src homology 3 (SH3) domain with a peptide fragment derived from a cDNA encoding a region of WASp-Interacting Protein (WIP) [9].
• TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition [10].
• Increased expression of WASP and WIP enhanced monocyte chemotaxis [11].
• Although the WASP homology 1 (WH1) domain of N-WASP interacts directly with WIP, we still lack the exact nature of its binding site [2].

Anatomical context of WIPF1

• By using the yeast two-hybrid system we have identified a proline-rich WASP-interacting protein (WIP), which coimmunoprecipitated with WASP from lymphocytes [12].
• CONCLUSIONS: WIP, a protein involved in filopodia formation, binds to both actin monomers and cortactin [9].
• Furthermore, WIP-knockdown experiments demonstrated that T cells with reduced WIP expression show a concordant reduction of WASP levels [13].
• Here we show that WASP gene transfer results in high WASP expression only when WIP is concomitantly expressed in K562 cells [13].
• Thus, the multiprotein complex is important for NK cell function, killer cell immunoglobulin-like receptor inhibitory signaling affects proteins involved in cytoskeletal rearrangements, and WIP plays a central role in the formation of the complex and in the regulation of NK cell activity [14].

Associations of WIPF1 with chemical compounds

• Interaction of the WH1 domain of N-WASP with WIP is dependent on the two highly conserved phenylalanine residues in the motif [2].
• The calpain inhibitor calpeptin increased WASP levels in activated T and B cells from the WASP patients, but not in primary T cells from the patients or from WIP(-/-) mice [15].
• Treatment with the proteasome inhibitors MG132 and bortezomib increased WASP levels in T cells from WIP(-/-) mice and in T and B lymphocytes from two WAS patients with missense mutations (R86H and T45M) that disrupt WIP binding [15].
• Our results show that WIP is essential both for the formation of actin cores containing WASP and cortactin and for the organization of integrin and integrin-associated proteins in circular arrays, specific characteristics of podosome structure [16].
• Deficiency of WASP, WIP or both did not interfere with selectin-dependent rolling or integrin-dependent adhesion of T cells in vitro [17].

Physical interactions of WIPF1

• GST-cortactin interacted with WIP in an SH3-dependent manner [9].
• We demonstrate the presence of profilin in Nck precipitates suggesting that Nck may couple extracellular signals to the cytoskeleton via its interaction with WIP and profilin [18].

Other interactions of WIPF1

• Lastly, coexpression of cortactin and WIP stimulated membrane protrusions [9].
• A role for WIP in cell polarity provides a framework for unifying, under a common paradigm, distinct molecular defects associated with immunodeficiencies like Wiskott-Aldrich syndrome [8].
• Our clone of this protein, termed WASP interacting protein (WIP) by others, shows a difference in seven amino acid residues, compared with the previously published sequence revealing an additional profilin binding motif [19].
• Identification of novel SH3 domain ligands for the Src family kinase Hck. Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1 [20].
• This report presents a novel WIP-like protein, WIRE (for WIP-related) [21].
• Third, a fusion protein of WIP to WASP efficiently mediates NFAT activation [22].

Analytical, diagnostic and therapeutic context of WIPF1

• Immunofluorescence localization of WIP in yeast cells reveals a pattern consistent with its function at the cortical sites of growth [8].
• The Microsphere Units from BRACE can be customer tailored to the materials and all necessary specifications as FDA, GMP/GLP, EX, CIP, WIP etc [23].
• Since 1985, the EEG has operated a network of air monitoring sites around WIPP and in nearby communities [24].

References