Role of the 14-3-3 C-terminal loop in ligand interaction

2002 ◽  
Vol 49 (3) ◽  
pp. 321-325 ◽  
Author(s):  
Amy B. Truong ◽  
Shane C. Masters ◽  
Hongzhu Yang ◽  
Haian Fu
Glycobiology ◽  
2021 ◽  
Author(s):  
Sabarinath Peruvemba Subramanian ◽  
Vairavan Lakshmanan ◽  
Dasaradhi Palakodeti ◽  
Ramaswamy Subramanian

Abstract O-Glycans on cell surfaces play important roles in cell-cell, cell-matrix, and receptor-ligand interaction. Therefore, glycan-based interactions are important for tissue regeneration and homeostasis. Free-living flatworm Schmidtea mediterranea, because of its robust regenerative potential, is of great interest in the field of stem cell biology and tissue regeneration. Nevertheless, information on the composition and structure of O-glycans in planaria is unknown. Using mass spectrometry and in silico approaches, we characterized the glycome and the related transcriptome of mucin-type O-glycans of planarian S. mediterranea. Mucin-type O-glycans were composed of multiple isomeric, methylated, and unusually extended mono- and di-substituted O-GalNAc structures. Extensions made of hexoses and 3-O methyl hexoses were the glycoforms observed. From glycotranscriptomic analysis, sixty genes belonging to five distinct enzyme classes were identified to be involved in mucin-type O-glycan biosynthesis. These genes shared homology with those in other invertebrate systems. While a majority of the genes involved in mucin-type O-glycan biosynthesis was highly expressed during organogenesis and in differentiated cells, a few select genes in each enzyme class were specifically enriched during early embryogenesis. Our results indicate a unique temporal and spatial role for mucin-type O-glycans during embryogenesis and organogenesis and in adulthood. In summary, this is the first report on O-glycans in planaria. This study expands the structural and biosynthetic possibilities in cellular glycosylation in the invertebrate glycome and provides a framework towards understanding the biological role of mucin-type O-glycans in tissue regeneration using planarians.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3583
Author(s):  
Stefania Mantovani ◽  
Stefania Varchetta ◽  
Dalila Mele ◽  
Matteo Donadon ◽  
Guido Torzilli ◽  
...  

Natural killer (NK) cells play a pivotal role in cancer immune surveillance, and activating the receptor/ligand interaction may contribute to control the development and evolution of hepatocellular carcinoma (HCC). We investigated the role of the natural killer group 2 member D (NKG2D) activating receptor and its ligand, the major histocompatibility complex class I chain-related protein A and B (MICA/B) in patients with cirrhosis and HCC subjected to surgical resection, patients with cirrhosis and no HCC, and healthy donors (HD). The NKG2D-mediated function was determined in peripheral blood (PB), in tumor-infiltrating lymphocytes (NK-TIL), and in matched surrounding liver tissue (NK-LIL). A group of patients treated with sorafenib because of clinically advanced HCC was also studied. A humanized anti-MICA/B monoclonal antibody (mAb) was used in in vitro experiments to examine NK cell-mediated antibody-dependent cellular cytotoxicity. Serum concentrations of soluble MICA/B were evaluated by ELISA. IL-15 stimulation increased NKG2D-dependent activity which, however, remained dysfunctional in PB NK cells from HCC patients, in line with the reduced NKG2D expression on NK cells. NK-TIL showed a lower degranulation ability than NK-LIL, which was restored by IL-15 stimulation. Moreover, in vitro IL-15 stimulation enhanced degranulation and interferon-γ production by PB NK from patients at month one of treatment with sorafenib. Anti-MICA/B mAb associated with IL-15 was able to induce PB NK cytotoxicity for primary HCC cells in HD and patients with HCC, who also showed NK-TIL degranulation for autologous primary HCC cells. Our findings highlight the key role of the NKG2D-MICA/B axis in the regulation of NK cell responses in HCC and provide evidence in support of a potentially important role of anti-MICA/B mAb and IL-15 stimulation in HCC immunotherapy.


2004 ◽  
Vol 78 (6) ◽  
pp. 799-806 ◽  
Author(s):  
Ryosuke Minagawa ◽  
Shinji Okano ◽  
Yukihiro Tomita ◽  
Kenji Kishihara ◽  
Hisakata Yamada ◽  
...  

Biopolymers ◽  
2007 ◽  
Vol 86 (5-6) ◽  
pp. 447-462 ◽  
Author(s):  
Dung Le-Nguyen ◽  
Laurent Chiche ◽  
François Hoh ◽  
Marie France Martin-Eauclaire ◽  
Christian Dumas ◽  
...  

1993 ◽  
Vol 5 (6) ◽  
pp. 963-967 ◽  
Author(s):  
Ramsay Fuleihan ◽  
Narayanaswamy Ramesh ◽  
Raif S. Geha

1997 ◽  
Vol 185 (5) ◽  
pp. 893-900 ◽  
Author(s):  
Elizabeth W. Shores ◽  
Tom Tran ◽  
Alexander Grinberg ◽  
Connie L. Sommers ◽  
Howard Shen ◽  
...  

Immature thymocytes undergo a selection process within the thymus based on their T cell antigen receptor (TCR) specificity that results either in their maturation into functionally competent, self-MHC–restricted T cells (positive selection) or their deletion (negative selection). The outcome of thymocyte selection is thought to be controlled by signals transduced by the TCR that vary in relation to the avidity of the TCR–ligand interaction. The TCR is composed of four distinct signal transducing subunits (CD3-γ, -δ, -ε, and ζ) that contain either one (CD3-γ, -δ, -ε) or three (-ζ) signaling motifs (ITAMs) within their intracytoplasmic domains. A possible function for multiple TCR ITAMs could be to amplify signals generated by the TCR during selection. To determine the importance of the multiple TCR-ζ chain ITAMs in thymocyte selection, transgenes encoding α/βTCRs with known specificity were bred into mice in which ζ chains lacking one or more ITAMs had been genetically substituted for endogenous ζ. A direct relationship was observed between the number of ζ chain ITAMs within the TCR complex and the efficiency of both positive and negative selection. These results reveal a role for multiple TCR ITAMs in thymocyte selection and identify a function for TCR signal amplification in formation of the T cell repertoire.


2017 ◽  
Author(s):  
Matthew S. Graus ◽  
Michael J. Wester ◽  
Douglas W. Lowman ◽  
David L. Williams ◽  
Michael D. Kruppa ◽  
...  

AbstractN-linked mannans (N-mannans) in the cell wall of Candida albicans are thought to mask β-(1,3)-glucan from recognition by Dectin-1, contributing to innate immune evasion. Lateral cell wall exposures of glucan on Candida albicans are predominantly single receptor-ligand interaction sites and are restricted to nanoscale geometries. Candida species exhibit a range of basal glucan exposures and their mannans also vary in size and complexity at the molecular level. We used super resolution fluorescence imaging and a series of protein mannosylation mutants in C. albicans and C. glabrata to investigate the role of specific N-mannan features in regulating the nanoscale geometry of glucan exposure. Decreasing acid labile mannan abundance and α-(1,6)-mannan backbone length correlated most strongly with increased density and nanoscopic size of glucan exposures in C. albicans and C. glabrata, respectively. Additionally, a C. albicans clinical isolate with high glucan exposure produced similarly perturbed N-mannan structures and exhibited similar changes to nanoscopic glucan exposure geometry. We conclude that acid labile N-mannan controls glucan exposure geometry at the nanoscale. Furthermore, variations in glucan nanoexposure characteristics are clinically relevant and are likely to impact the nature of the pathogenic surface presented to innate immunocytes at dimensions relevant to receptor engagement, aggregation and signaling.


1998 ◽  
Vol 66 (2) ◽  
pp. 603-607 ◽  
Author(s):  
Mary Cosyns ◽  
Svetlana Tsirkin ◽  
Michelle Jones ◽  
Richard Flavell ◽  
Hitoshi Kikutani ◽  
...  

ABSTRACT Mice with disrupted genes for CD40 and CD40 ligand (CD40L) are unable to clear infection with Cryptosporidium parvum and develop cholangitis. Parasites are present in the gut, gall bladder, and biliary tree, and biliary epithelial cells express CD40 on the cell surface. SCID mice infected with C. parvum for >1 month can clear the infection after reconstitution with spleen cells from CD40, but not CD40L, knockout mice. In an in vitro model, C. parvum-infected HepG2 cells were triggered to apoptosis when incubated with a CD40L-CD8 fusion protein. The requirement for CD40-CD40L interactions for immunity to C. parvum indicated by our results may entail the triggering of apoptosis in infected cells, in addition to the known role of CD40L-CD40 interactions in stimulating cytokine production and promoting T-cell responses.


2001 ◽  
Vol 33 (1-2) ◽  
pp. 283 ◽  
Author(s):  
R Minagawa ◽  
S Okano ◽  
Y Tomita ◽  
I Shimizu ◽  
T Iwai ◽  
...  

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