Bovine leukemia virus gp30 transmembrane (TM) protein is not tyrosine phosphorylated: examining potential interactions with host tyrosine-mediated signaling

Hamilton, Valerie T.; Stone, Diana M.; Pritchard, Suzanne M.; Cantor, Glenn H.

doi:10.1016/s0168-1702(02)00149-1

Cited by 11 publications

(10 citation statements)

References 89 publications

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“…BLV Env proteins were not detectably phosphorylated in infected cells constitutively producing virus (Fig. 7), in agreement with results obtained by others using two different virusproducing, non-lymphoid cell lines (23). A difficulty with interpreting these results is that viral or cellular mutations could have occurred during the derivation of virus-producing cell lines and such a change might preclude phosphorylation of the CTM.…”

Section: Resultssupporting

confidence: 91%

“…The cytoplasmic tail of BLV TM may become phosphorylated at tyrosine and interact with SHP-1 only in virus-infected primary cells and only at certain stages of infection, because in some infected animals, no association of SHP-1 with TM could be detected (11). Disappointingly, systematic attempts to demonstrate phosphorylation of BLV TM in infected cells from infected animals have been unsuccessful (23). Success in such an endeavor may require replication of cell-cell signaling interactions that occur when BLV is being produced by B cells in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…The YXXL motifs within the membrane-proximal ITAM could also be part of immunoreceptor tyrosine-based inhibi-tion motifs (ITIMs) (23) having the sequences SXYXXL and IYSXL (57,59). Upon phosphorylation of the tyrosine residues, ITIM-containing proteins are bound by SH2 domains, for example, in phosphatases and signaling is inhibited (reviewed in reference 23).…”

mentioning

confidence: 99%

“…Moreover, replacement of the second tyrosine residue with alanine greatly reduces the propagation and infectivity of the virus in cultured fetal lamb kidney cells (27). Although propagation of signals by ITAMs and ITIMs depends on phosphorylation of their tyrosine residues, BLV TM has not been found to be phosphorylated at tyrosine when peripheral blood mononuclear cells from infected cows are cultured briefly to allow virus expression and synthesis of the Env protein (23).…”

mentioning

confidence: 99%

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Dileucine and YXXL Motifs in the Cytoplasmic Tail of the Bovine Leukemia Virus Transmembrane Envelope Protein Affect Protein Expression on the Cell Surface

Novakovic

Sawai

Radke

2004

J Virol

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Several retroviruses downmodulate the cell surface expression of envelope (Env) proteins through peptide sequences located in the cytoplasmic tail of the transmembrane (TM) subunit. We investigated whether cell surface expression of a chimeric protein containing the cytoplasmic domain of the TM protein (CTM) of bovine leukemia virus (BLV) was regulated by two membrane-proximal dileucine motifs or by tyrosine Y487 or Y498 in YXXL motifs. A chimeric protein composed of the extracellular and membrane-spanning portions of human CD8-␣ plus a wild-type (wt) BLV CTM was detectable on the surface of only 40% of the cells in which it was transiently expressed. Replacement of either dileucine pair with alanines increased the level of surface display of chimeric proteins. Nearly all cells became surface positive when both dileucine motifs were altered simultaneously and when either an N-terminal segment containing both dileucine motifs or a C-terminal segment containing all YXXL motifs was deleted. In contrast, replacement of Y487 or Y498 with alanine or phenylalanine enabled only small increases in surface display compared with wt levels. Chimeric proteins had similar stabilities but were downmodulated from the cell surface at three different rates. Point mutants segregated into each of the three groups of proteins categorized according to these different rates. Interestingly, Y487 mutants were downmodulated less efficiently than Y498 mutants, which behaved like wt. CD8-CTM chimeric proteins were phosphorylated on serine residues, but the native BLV Env protein was not phosphorylated either in transfected cells or in a lymphoid cell line constitutively producing BLV. Thus, both dileucine and YXXL motifs within the BLV CTM contribute to downmodulation of a protein containing this domain. Interactions with other proteins may influence surface exposure of Env protein complexes in virus-infected cells, assisting in viral evasion of adaptive immunity.The cytoplasmic domains of several retroviral envelope (Env) proteins control the level of Env present on the surface of infected cells. A low level of surface expression is mediated by intracellular retention of Env proteins as well as their rapid endocytosis from the plasma membrane (22,51,54). The existence of mechanisms to ensure low-level cell surface display of Env proteins points to a feature of the retroviral life cycle that most probably evolved to reduce clearance of virus-producing cells by the immune system (21, 22, 35). The main target for antibody recognition of retroviral Env protein complexes is the surface (SU) protein subunit, which is anchored onto the membranes of infected cells and virions by the membrane-spanning domain of the transmembrane (TM) subunit of an Env monomer (26). A labile disulfide bond links the SU and TM subunits of bovine leukemia virus (BLV) (30), a deltaretrovirus. Upon binding of oligomers of retroviral SU to cellular receptors, the TM subunits mediate virus-cell fusion (26). In parallel with other retroviral TM proteins, the extracellular...

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Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dileucine and YXXL Motifs in the Cytoplasmic Tail of the Bovine Leukemia Virus Transmembrane Envelope Protein Affect Protein Expression on the Cell Surface

Novakovic

Sawai

Radke

2004

J Virol

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“…The BLV TM acts as a fusion protein and inserts in cell membranes. It also acts in signal transduction through immunoreceptor tyrosine-based activation motifs to transduce signals through the cell membranes, is required for infectivity in vivo (44), and contains typical proline-rich motifs (PXXP) important for the maintenance of typical viral loads in vivo (45). In addition, BLV TM interacts with phosphatase SHP-1 and acts as a critical negative regulator of B cell receptor signaling (46,47).…”

Section: Blv and Htlv-1 Gene Products And Their Role In Pathogenesismentioning

confidence: 99%

Animal Models of Bovine Leukemia Virus and Human T-Lymphotrophic Virus Type-1: Insights in Transmission and Pathogenesis

Lairmore

2014

Annu. Rev. Anim. Biosci.

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Bovine leukemia virus (BLV) and human T-lymphotrophic virus type-1 (HTLV-1) are related retroviruses associated with persistent and lifelong infections and a low incidence of lymphomas within their hosts. Both viruses can be spread through contact with bodily fluids containing infected cells, most often from mother to offspring through breast milk. Each of these complex retroviruses contains typical gag, pol, and env genes but also unique, nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the pathogenesis of each virus. Comparisons of BLV and HTLV-1 provide insights into mechanisms of spread and tumor formation, as well as potential approaches to therapeutic intervention against the infections.

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Enteropathogenic Escherichia coli Recruits the Cellular Inositol Phosphatase SHIP2 to Regulate Actin-Pedestal Formation

Smith

Humphreys

Hume

et al. 2010

Cell Host & Microbe

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Adhesion of enteropathogenic Escherichia coli to epithelial cells triggers actin-rich pedestal formation beneath the bacteria. Pedestal formation requires delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane. The C-terminal regions in Tir, encompassing Y483 and Y511, share sequence similarity with cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs), which are critical regulators of eukaryotic signaling pathways. We demonstrate that Y483 and Y511 within tandem ITIM-like sequences are essential for recruiting SHIP2, a host inositol phosphatase. SHIP2 controls condensed F-actin-pedestal formation by engaging the adaptor SHC and by generating a PI(3,4)P(2)-enriched lipid platform for recruitment of the cytoskeletal regulator lamellipodin. Therefore, mimicry of eukaryotic receptor motifs by Tir controls both the lipid and protein composition of the signaling platform necessary for pedestal formation. Further, the dual action of SHIP2's scaffolding and phosphatase functions ensures tight compartmentalization and coordination of actin dynamics during pedestal formation.

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Bovine leukemia virus gp30 transmembrane (TM) protein is not tyrosine phosphorylated: examining potential interactions with host tyrosine-mediated signaling

Cited by 11 publications

References 89 publications

Dileucine and YXXL Motifs in the Cytoplasmic Tail of the Bovine Leukemia Virus Transmembrane Envelope Protein Affect Protein Expression on the Cell Surface

Dileucine and YXXL Motifs in the Cytoplasmic Tail of the Bovine Leukemia Virus Transmembrane Envelope Protein Affect Protein Expression on the Cell Surface

Animal Models of Bovine Leukemia Virus and Human T-Lymphotrophic Virus Type-1: Insights in Transmission and Pathogenesis

Enteropathogenic Escherichia coli Recruits the Cellular Inositol Phosphatase SHIP2 to Regulate Actin-Pedestal Formation

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