p56lck protein-tyrosine kinase is cytoskeletal and does not bind to polyomavirus middle T antigen

Louie, Rikah; King, C S; MacAuley, A; Marth, Jamey D.; Perlmutter, Roger M.; Eckhart, Walter; Cooper, Jonathan A.

doi:10.1128/jvi.62.12.4673-4679.1988

Cited by 41 publications

(15 citation statements)

References 55 publications

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“…p56 lck constitutively associates with CD4 through a conserved cysteine motif [27,28] and this interaction prevents CD4 from entering coated pits [10]. Studies with p56 lck mutants suggest that p56 lck binding does not simply mask an endocytosis signal on the cytoplasmic domain of CD4 [10], but has additional effects, perhaps anchoring CD4 to the cytoskeleton [29].…”

Section: Discussionmentioning

confidence: 99%

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

et al. 1998

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In cell lines the endocytic properties of CD4 are regulated through its association with the src-family tyrosine kinase p56lck . In lymphoid cell lines expressing p56 lck , CD4 is restricted to the cell surface and undergoes only limited internalization. Phosphorylation of the cytoplasmic domain of CD4 causes p56 lck to dissociate and activates an endocytosis signal leading to the internalization of CD4 through clathrin-coated pits. In p56 lck -negative transfected cell lines CD4 is constitutively internalized, but internalization is inhibited when p56 lck is expressed in these cells. We now demonstrate that these endocytic properties of CD4 determined in transfected cell lines hold true for CD4 naturally expressed on myeloid cell lines (HL-60 and U937), as well as on primary lymphocytes, monocytes and macrophages isolated from human blood. CD4 showed limited internalization on p56 lck -positive lymphocytes, but was rapidly internalized in p56 lck -negative monocytes and macrophages. Surprisingly, rapid internalization of CD4 was seen with the lymphocytes from one unidentified donor. In these cells we failed to detect p56 lck expression by Western blotting.

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Section: Discussionmentioning

confidence: 99%

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

et al. 1998

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“…Key regulatory tyrosine residues are conserved in p56' '' " as position 505 in the C-terminus and at the autophosphorylation site of residue 394 (Marth et al 1985, Voronova & Sefton 1986, Trevillyan et al 1986a, Koga et al 1986). Aberrant forms of p56''='' with mutations at tyrosine 505 have been shown to transform cells due to an increase in tyrosine kinase activity (Amrein & Sefton 1988, Marth et al 1988). In addition, abnormally high levels of Ick expression have t>een shown to occur naturally in the murine thymic lymphoma.…”

Section: A Cd4/cd8:p56'=^-mediated Pathway Of T-cell Activationmentioning

confidence: 99%

Molecular Interactions, T‐Cell Subsets and a Role of the CD4/CD8:p56^lck Complex in Human T‐Cell Activation

Rudd

Anderson

Morimoto

et al. 1989

Immunological Reviews

114

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Several T-cell structures are capable of generating intracellular signals linked to T-cell proliferation. Crosslinking of CD2, CD4 and CD45 with Ti/CD3 to several of these antigens can augment the minimal signal induced by antigen binding to the Ti/CD3 complex. Importantly, some of these regulatory structures (CD4, CD8 and CD45) are also expressed on subsets of T cells with distinct activation requirements and functional programs (helper, suppressor, suppressor-inducer and cytotoxic function). The CD4+ CD45RA+ (2H4+) subset responds well to self-Ia, poorly to soluble antigen and possesses suppressor-inducer function. A reciprocal subset CD4+ CD45RA- (4B4+) is preferentially activated by soluble recall antigens and possesses helper function. Each of these subsets can be distinguished by virtue of the differential expression of CD45 antigens. Importantly, the anti-2H4 antibody which reacts with a specific region near the N-terminus of two CD45 isoforms can effectively block its function. Crosslinking of CD4 with the Ti/CD3 complex preferentially activated the CD4+ CD45+ RA- subset, while soluble antibodies to CD2 preferentially affected the CD45 CD45RA+ subset. Thus, CD3 and CD4 more effectively synergize in the activation process on the CD4+ CD45RA- subset, a result consistent with the ability of this subpopulation to respond to recall antigens. The regulatory role of the CD4, CD8 and CD45 antigens may be mediated by an interactive network of protein-tyrosine phosphorylation and dephosphorylation. We have shown the CD4 and CD8 antigens to be associated with the T cell-specific protein-tyrosine kinase (p56lck). p56lck is a member of a family of protein-tyrosine kinases with an established ability to activate and transform mammalian cells. The CD4/CD8:p56lck complex is catalytically active as shown by its ability to phosphorylate various members of the Ti/CD3 complex. By contrast, the CD45 antigens possess protein-tyrosine phosphatase activity within their intracellular domains and are postulated to function by virtue of a regulatory interaction with CD4/CD8:p56lck and its potential substrates. Thus, the differences in the response of the CD4+ CD45RA+/- subsets to various stimuli and the expansion of T-cell subsets with distinct immunoregulatory programs may be governed by a pathway of tyrosine-mediated events.

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“…The Src-homology (SH)2 and SH3 domains of Lck are essential for regulating cellular localization [50] and activation of its catalytic domain [51]. In T cells, Lck is found in the plasma membrane, associated with the receptors CD4 and CD8 [52]. The c-Src kinase (Csk) phosphorylates Y505 of Lck, resulting in the reduction of Lck catalytic activity [53].…”

Section: Lckmentioning

confidence: 99%

TRAF3 as a regulator of T lymphocyte activation

Wallis¹

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T cells are an essential component of the adaptive immune system, which evolved to facilitate development of long-term, effective protection against infectious diseases. Upon activation, T cells play an important role in clearing infections, and especially, in preventing establishment of subsequent infections with the same pathogen. Because this is such a powerful response, it must be tightly regulated. Our lab has long been interested in how signaling molecules regulate the function of T and B lymphocytes. Our prior studies stimulated an interest in the signaling adapter molecule, Tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3). Our group previously produced a T cellconditional (CD4-Cre) TRAF3-/mouse, which demonstrated that TRAF3 unexpectedly plays an important positive role in T cell functions, including providing help for B cell responses, protection from infectious pathogens, cytokine production and proliferation. After TCR engagement, TRAF3 associates with the T Cell Receptor (TCR)/CD28 complex. These data identified a new role for TRAF3 in T cell activation. There are three signals that are required for full T cell activation. The three types of receptors that deliver these signals are the TCR, co-stimulatory receptors and cytokine receptors. This dissertation explores the regulatory role of TRAF3 in the 3 signals required for T cellsactivation. In signal 1, TRAF3 enhances TCR signaling by regulating the localization of the TCR inhibitors, PTPase non-receptor type 22 (PTPN22) and the c-Src kinase (Csk). Our lab previously reported that recruitment of TRAF3 to the TCR complex requires co-stimulation of CD28, the primary receptor for signal 2. In this dissertation, we show that TRAF3 associates with the Linker of Activated T cells (LAT) complex, demonstrating preference for distinct LAT-associated proteins. For delivery of vii signal 3, T cells require stimulation of a cytokine receptor, such as IFNR, for differentiation of a T cell to an effector cell. Upon IFN stimulation, TRAF3 inhibits IFNR-induced early molecular events, which results in the regulation of both canonical and non-canonical IFNR signaling pathways. The results presented in this dissertation highlight the dynamic roles of TRAF3 as a regulator of T cell activation, by regulating multiple T cell signaling pathways.

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p56lck protein-tyrosine kinase is cytoskeletal and does not bind to polyomavirus middle T antigen

Cited by 41 publications

References 55 publications

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

Molecular Interactions, T‐Cell Subsets and a Role of the CD4/CD8:p56^lck Complex in Human T‐Cell Activation

TRAF3 as a regulator of T lymphocyte activation

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p56lck protein-tyrosine kinase is cytoskeletal and does not bind to polyomavirus middle T antigen

Cited by 41 publications

References 55 publications

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

Lack of p56 lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells

Molecular Interactions, T‐Cell Subsets and a Role of the CD4/CD8:p56lck Complex in Human T‐Cell Activation

TRAF3 as a regulator of T lymphocyte activation

Contact Info

Product

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Molecular Interactions, T‐Cell Subsets and a Role of the CD4/CD8:p56^lck Complex in Human T‐Cell Activation