The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes.

Rudd, Christopher E.; Trevillyan, James M.; Dasgupta, Jai Dev; Wong, Linda L.; Schlossman, Stuart F.

doi:10.1073/pnas.85.14.5190

Cited by 656 publications

(331 citation statements)

References 46 publications

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“…A potential function for the Ick gene in signal transduction in lymphocytes was initially postulated on the basis of its physical association with the membrane glycoproteins CD4 and CD8 (8,27,34). Consistent with this hypothesis, crosslinking of CD4 with antibodies activates the protein kinase activity of lck (35).…”

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confidence: 57%

“…Immunoprecipitates were also treated with calf intestinal alkaline phosphatase (Boehringer) and potato acid phosphatase (Boehringer) as described previously (22). In the in vitro kinase assay (27), PBS-washed cells were lysed in 2% Nonidet P-40 and TEN (50 mM Tris-HCl [pH 7.4], 1 mM EDTA, 0.15 M NaCl). Immunoprecipitated proteins were suspended in 10 ,ul of kinase buffer containing 50 mM piperazine-N,N'-bis(2-ethanesulfonic acid) (PIPES; pH 7.0), 1 mM MnCl, 1 mM Na3VO4, and 10 ,uCi of [.y-32P]ATP) and incubated at room temperature for 20 min.…”

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confidence: 99%

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Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Yi¹,

Bolen²,

Ihle³

1991

Mol. Cell. Biol.

146

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confidence: 57%

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confidence: 99%

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Yi¹,

Bolen²,

Ihle³

1991

Mol. Cell. Biol.

146

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“…In mature T-cells, the majority of Lck is associated with cell surface CD4 or CD8 (Rudd et al, 1988;Veillette et al, 1988), the coreceptors of the T-cell receptor complex, but other membrane-binding partners may be used with low stoichiometry or during the early phases of T cell ontogeny (Rudd et al, 1993). However, in all cases the functional activity of Lck is dependent on its ability to associate with the cytoplasmic face of cellular membranes (Yurchak and Sefton, 1995;Yurchak et al, 1996;Kabouridis et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Hsp90 Is Essential for the Synthesis and Subsequent Membrane Association, But Not the Maintenance, of the Src-Kinase p56^lck

Bijlmakers

Marsh

2000

MBoC

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Tyrosine kinases of the Src family are synthesized as cytosolic proteins that subsequently translocate to membranes. Little is known of the mechanisms responsible for targeting these proteins to membranes, although a role for the cytosolic chaperone Hsp90 has been proposed. Here, we have studied the involvement of Hsp90 in the synthesis, membrane binding, and maintenance of the Src-kinase Lck. Using specific inhibitors of Hsp90, geldanamycin and radicicol, we found that functional Hsp90 is essential for the stability of newly synthesized, but not mature, Lck. Similar results were obtained for two other Src-kinases, c-Src and Lyn. In contrast, LckY505F and LckΔSH2, constitutively active Lck mutants lacking the C-terminal regulatory tyrosine or the entire Src homology 2 domain, respectively, required Hsp90 activity to stabilize the mature proteins. Lck synthesized in the absence of Hsp90 activity was degraded within 30–45 min. This unstable Lck was myristoylated normally but did not associate with membranes or CD4, interactions that normally start within minutes of the completion of Lck synthesis. A construct composed of the N-terminal unique domain of Lck fused to green fluorescent protein did not require Hsp90 activity during synthesis. In addition, this protein associated with membranes efficiently in the absence of Hsp90 activity. Together these data suggest that interaction with Hsp90 is necessary for the correct synthesis and subsequent membrane binding of Lck. However, Hsp90 does not appear to play a direct role in Lck membrane, or CD4, association.

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“…Support for this notion has come from the identification of a src tyrosine kinase, p56 ~k, which associates with the cytoplasmic tail of CD4 (33)(34)(35). Induction of CD4-TCR association with certain anticlonotypic antibodies (36) or in vitro kinase assays with p56~k-immunoprecipitates (29) results in the phosphorylation of CD3e and CD3~" (also known as TCR~).…”

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confidence: 99%

Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor.

Vignali

Strominger

1994

The Journal of Experimental Medicine

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StlmmaryHen egg lysozyme 52-61-specific CD4 + T cells responded by interleukin 2 (IL-2) secretion to any peptide containing this epitope regardless of length of NH2-and COOH-terminal composition. However, CD4-variants could only respond to peptides containing the two COOHterminal tryptophans at positions 62 and 63. Substitutions at these positions defined patterns of reactivity that were specific for individual T cells inferring a T cell receptor (TCR)-based phenomenon. Thus, the fine specificity of major histocompatibility complex (MHC)-peptide recognition by the TCR was dramatically affected by CD4 and the COOH-terminal peptide composition. Peptides that failed to induce IL-2 secretion in the CD4-variants nevertheless induced strong tyrosine phosphorylation of CD3~'. Thus, whereas the TCR still recognized and bound to the MHC class II-peptide complex resulting in protein phosphorylation, this interaction failed to induce effective signal transduction manifested by IL-2 secretion. This provides a dear example of differential signaling mediated by peptides known to be naturally processed. In addition, the external domains of CD4, rather than its cytoplasmic tail, were critical in aiding TCK recognition of all peptides derived from a single epitope. These data suggest that the nested flanking residues, which are present on MHC class II but not class I bound peptides, are functionally relevant.

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The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes.

Cited by 656 publications

References 46 publications

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Hsp90 Is Essential for the Synthesis and Subsequent Membrane Association, But Not the Maintenance, of the Src-Kinase p56^lck

Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor.

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The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes.

Cited by 656 publications

References 46 publications

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus.

Hsp90 Is Essential for the Synthesis and Subsequent Membrane Association, But Not the Maintenance, of the Src-Kinase p56lck

Amino acid residues that flank core peptide epitopes and the extracellular domains of CD4 modulate differential signaling through the T cell receptor.

Contact Info

Product

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About

Hsp90 Is Essential for the Synthesis and Subsequent Membrane Association, But Not the Maintenance, of the Src-Kinase p56^lck