Activation of a tyrosine protein kinase is an early event in the stimulation of T lymphocytes by interleukin-2.

The ability of the T lymphocyte growth factor interleukin 2 (IL-2) to activate a tyrosine protein kinase in vivo was assessed by using antibodies to phosphotyrosine in conjunction with immunoblots. Treatment of the murine IL-2-dependent cytotoxic T cell line CTLL-2 with IL-2 resulted in an increase in tyrosine phosphorylation of several proteins of molecular weights ranging from 38,000 to 120,000. The tyrosine phosphorylation in the various proteins increased in a concomitant fashion and reached a maximum level within 15 min. The concentration of IL-2 required for inducing this phosphorylation was similar to that required for stimulating [3H]thymidine uptake, indicating that the increase in tyrosine phosphorylation correlated with the ability of IL-2 to stimulate the proliferation of the CTLL-2 cells. IL-2 was also found to induce the phosphorylation of proteins on tyrosine residues in short term cultures of human T lymphocytes. These results suggest that IL-2, like other polypeptide growth factors, acts by stimulating the activity of a tyrosine protein kinase.

• Publication year

  1988

• Venue

  Journal of Biological Chemistry

• Publication date

  1988-05-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0021-9258(18)68588-6PMID 3259228
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Demonstration that LSTRA cells have an elevated level of proteins phosphorylated on tyrosine residues

  1987cited by this paper
• Detection of phosphotyrosine-containing proteins in polyomavirus middle tumor antigen-transformed cells after treatment with a phosphotyrosine phosphatase inhibitor

  1987cited by this paper
• Molecular mechanisms involved in T cell activation. II. The phosphatidylinositol signal-transducing mechanism mediates antigen-induced lymphokine production but not interleukin 2-induced proliferation in cloned cytotoxic T lymphocytes.

  1987cited by this paper
• Interleukin 2 rapidly stimulates synthesis and breakdown of polyphosphoinositides in interleukin 2-dependent, murine T-cell lines.

  1987cited by this paper
• Stimulation of specific GTP binding and hydrolysis activities in lymphocyte membrane by interleukin-2

  1987cited by this paper
• The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells.

  1987cited by this paper
• Signals for activation and proliferation of murine T lymphocyte clones.

  1987cited by this paper
• Interleukin 2 high-affinity receptor expression requires two distinct binding proteins

  1987cited by this paper
• Direct activation of human resting T cells by IL 2: the role of an IL 2 receptor distinct from the Tac protein.

  1987cited by this paper
• Multiple kinases and signal transduction. Phosphorylation of the T cell antigen receptor complex.

  1987cited by this paper
• Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors.

  1987cited by this paper
• Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex.

  1986cited by this paper
• Interleukin 2 does not induce phosphatidylinositol hydrolysis in activated T cells.

  1986cited by this paper
• Conversion of low-affinity interleukin 2 receptors to a high-affinity state following fusion of cell membranes.

  1986cited by this paper
• Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes.

  1986cited by this paper
• Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions.

  1986cited by this paper
• Expression of functional human interleukin-2 receptor in mouse T cells by cDNA transfection

  1986cited by this paper
• Protein tyrosine phosphorylation in the cell cycle of BALB/c 3T3 fibroblasts.

  1986cited by this paper
• Phosphotyrosine antibodies identify the p210c-abl tyrosine kinase and proteins phosphorylated on tyrosine in human chronic myelogenous leukemia cells

  1986cited by this paper
• Stable expression of cDNA encoding the human interleukin 2 receptor in eukaryotic cells

  1985cited by this paper
• Reconstitution of functional receptor for human interleukin-2 in mouse cells

  1985cited by this paper
• Interleukin-2 stimulates association of protein kinase C with plasma membrane

  1985cited by this paper
• Distinction between antigen receptor and IL 2 receptor triggering events in the activation of alloreactive T cell clones with calcium ionophore and phorbol ester.

  1985cited by this paper
• Interleukin 2 regulates its own receptors.

  1985cited by this paper
• Isolation of antibodies for phosphotyrosine by immunization with a v-abl oncogene-encoded protein

  1985cited by this paper
• Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen

  1984cited by this paper
• Interleukin 2: the molecule and its function.

  1984cited by this paper
• Molecular cloning of cDNA encoding human interleukin-2 receptor

  1984cited by this paper
• Molecular cloning and expression of cDNAs for the human interleukin-2 receptor

  1984cited by this paper
• Use of an antiserum against phosphotyrosine for the identification of phosphorylated components in human fibroblasts stimulated by platelet-derived growth factor.

  1984cited by this paper
• Diverse mitogenic agents induce the phosphorylation of two related 42,000-dalton proteins on tyrosine in quiescent chick cells

  1984cited by this paper
• A tumor promoter stimulates phosphorylation on tyrosine.

  1983cited by this paper
• Phorbol ester and diacylglycerol induce protein phosphorylation at tyrosine

  1983cited by this paper
• Direct demonstration of the identity of T cell growth factor binding protein and the Tac antigen

  1983cited by this paper
• Transient expression of interleukin 2 receptors. Consequences for T cell growth

  1983cited by this paper
• Functional significance of Tac antigen expressed on activated human T lymphocytes: Tac antigen interacts with T cell growth factor in cellular proliferation.

  1982cited by this paper
• A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor

  1982cited by this paper
• T cell growth factor receptors. Quantitation, specificity, and biological relevance

  1981cited by this paper
• Spontaneous release of a factor with properties of T cell growth factor from a continuous line of primate tumor T cells.

  1981cited by this paper
• Continuous proliferation of murine antigen-specific helper T lymphocytes in culture

  1979cited by this paper
• Long term culture of tumour-specific cytotoxic T cells

  1977cited by this paper

• hck Phosphorylation and Activation of p59 IL-2 Signaling in Human Monocytes Involves

  2017cites this paper
• Interleukin-2 Gene Expression in Central Nervous System Cells after Stress and Antigen Application

  2008cites this paper
• Protein tyrosine phosphatases and the immune response

  2005cites this paper
• membrane-associated protein kinase

  2003cites this paper
• Interleukin-2 receptors and interleukin-2-mediated signaling in myelin: activation of diacylglycerol kinase and phosphatidylinositol 3-kinase.

  2003cites this paper
• CD 28 Ligation in T-cell Activation : Evidence for Two Signal Transduction Pathways

  2003cites this paper
• Signaling domains of the interleukin 2 receptor.

  2001cites this paper
• current as proteins in normal human T lymphocytes . The growth factor IL-2 activates p 21 ras

  2001cites this paper
• Association of STAT1, STAT3 and STAT5 proteins with the IL‐2 receptor involves different subdomains of the IL‐2 receptor β chain

  2000cites this paper
• IL-2 Signaling in Human Monocytes Involves the Phosphorylation and Activation of p59hck 1

  2000cites this paper
• Biochemical analysis of interleukin-2 receptor beta chain phosphorylation by p56(lck).

  1999cites this paper
• Biochemical analysis of interleukin‐2 receptor β chain phosphorylation by p56lck

  1999cites this paper
• Interleukin-2 induces beta2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB).

  1998cites this paper
• Tyrosine kinase substrates in interleukin-2 signaling.

  1998cites this paper
• Cell Cycle Progression STAT5 in Protection from Apoptosis But Not in Regulation of Cell Growth by IL-2: Role of

  1998cites this paper
• Regulation of cell growth by IL-2: role of STAT5 in protection from apoptosis but not in cell cycle progression.

  1998cites this paper
• A New Tyrosine-phosphorylated 97-kDa Adaptor Protein Mediates Interleukin-2-induced Association of SHP-2 with p85-Phosphatidylinositol 3-Kinase in Human T Lymphocytes*

  1998cites this paper
• Recent Advances in the Understanding of Interleukin-2 Signal Transduction

  1998cites this paper
• Signaling from the IL-2 receptor to the nucleus.

  1997cites this paper
• Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids.

  1997cites this paper
• The role of protein kinases in antigen-activation of peripheral blood mononuclear cells of Schistosoma mansoni infected individuals.

  1997cites this paper
• IL-15 promotes cytokine production of human T helper cells.

  1996cites this paper
• Interleukin-2 receptor signaling mechanisms.

  1996cites this paper
• A critical role of IL-2 for the production and gene transcription of IL-5 in allergen-specific human T cell clones.

  1996cites this paper
• Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling.

  1996cites this paper
• The common gamma-chain for multiple cytokine receptors.

  1995cites this paper
• Effects of protein tyrosine kinase inhibitors with different modes of action on topoisomerase activity and death of IL-2-dependent CTLL-2 cells.

  1995cites this paper
• Protein-tyrosine kinase-dependent activation of STAT transcription factors in interleukin-2- or interleukin-4-stimulated T lymphocytes

  1995cites this paper
• The Clinical and Experimental Use of Monoclonal Antibodies to the IL-2 Receptor

  1995cites this paper
• Regulation of apoptosis of interleukin 2‐dependent mouse T‐cell line protein tyrosine phosphorylation and polyamines

  1995cites this paper
• Involvement of JAK-family tyrosine kinases in hematopoietin receptor signal transduction.

  1994cites this paper
• Interleukin 2‐induced activation of JAK3: Possible involvement in signal transduction for c‐myc induction and cell proliferation

  1994cites this paper
• The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation.

  1994cites this paper
• Biochemistry of B lymphocyte activation.

  1994cites this paper
• The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line

  1994cites this paper
• Effects of Vanadate on Prostacyclin and Endothelin-1 Production and Protein-Tyrosine Phosphorylation in Human Endothelial Cells

  1994cites this paper
• A tyrosine phosphorylation requirement for cytotoxic T lymphocyte degranulation.

  1994cites this paper
• The cytoplasmic domain of the interleukin-2 receptor beta chain contains both unique and functionally redundant signal transduction elements.

  1994cites this paper
• Gene transfer of the interleukin (IL)‐2 receptor β chain into an IL‐7‐dependent pre‐B cell line permits IL‐2‐driven proliferation: Tyrosine phosphorylation of Shc is induced by IL‐2 but not IL‐7

  1994cites this paper
• Interleukin-2 and the interleukin-2 receptor complex.

  1994cites this paper
• Physical association of JAK1 and JAK2 tyrosine kinases with the interleukin 2 receptor beta and gamma chains.

  1994cites this paper
• MHC class I antigens regulate CD3-induced tyrosine phosphorylation of proteins in T cells.

  1994cites this paper
• MHC class II molecules regulate growth in human T cells.

  1994cites this paper
• Early lymphocyte activation events are inhibited by antiproliferative synthetic peptide 2438, a fragment of human interferon alpha-2, and immunosuppressant cyclosporine A.

  1994cites this paper
• Signal transduction mediated by the reconstituted IL-2 receptor. Evidence for a cell type-specific function of IL-2 receptor beta-chain.

  1994cites this paper
• Direct stimulation of Vav guanine nucleotide exchange activity for Ras by phorbol esters and diglycerides

  1994cites this paper
• Pervanadate simulates the effects of interleukin-2 (IL-2) in human T cells and provides evidence for the activation of two distinct tyrosine kinase pathways by IL-2.

  1994cites this paper
• Cytokine-enhanced NK cell-mediated cytotoxicity. Positive modulatory effects of IL-2 and IL-12 on stimulus-dependent granule exocytosis.

  1994cites this paper
• SH2-dependent association of phosphatidylinositol 3'-kinase 85-kDa regulatory subunit with the interleukin-2 receptor beta chain.

  1994cites this paper
• Severe combined immunodeficiency, interleukin-2 (IL-2), and the IL-2 receptor: experiments of nature continue to point the way.

  1994cites this paper
• Interleukin-2-induced tyrosine phosphorylation of p52shc in T lymphocytes.

  1993cites this paper
• Novel mechanism for inhibition of human T cells by glucocorticoids. Glucocorticoids inhibit signal transduction through IL-2 receptor.

  1993cites this paper
• Anti-CD2-induced tyrosine phosphorylation of T cell polypeptides is independent of the PMA-induced modification of p56lck.

  1993cites this paper
• Tyrosine kinase(s) regulate apoptosis and bcl-2 expression in a growth factor-dependent cell line.

  1993cites this paper
• Introduction to cytokine receptors: structure and signal transduction.

  1993cites this paper
• Tyrosine phosphorylation and dephosphorylation in T lymphocyte activation.

  1993cites this paper
• Gangliosides inhibit T-lymphocyte proliferation by preventing the interaction of interleukin-2 with its cell surface receptors.

  1993cites this paper
• Lowest dose interleukin-2 immunotherapy.

  1993cites this paper
• Murine T-lymphocyte proliferation induced by interleukin 2 correlates with a transient increase in p56lck kinase activity and the tyrosine phosphorylation of a 97-kDa protein.

  1993cites this paper
• Relationship between apoptosis and the cell cycle in lymphocytes: roles of protein kinase C, tyrosine phosphorylation, and AP1.

  1993cites this paper
• Activation of mitogen-activated protein kinase/ERK-2 in phytohaemagglutin in blasts by recombinant interleukin-2: contrasting features with CD3 activation.

  1993cites this paper
• MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors.

  1993cites this paper
• Induction of Interleukin 2‐Responsiveness in Thymocytes of the Transgenic Mice Carrying lck‐Transgene

  1993cites this paper
• Tyrosine phosphorylation of a 100-kDa protein is correlated with cytotoxic T-lymphocyte function. Evidence from cis unsaturated fatty acid and phenylarsineoxide inhibition.

  1993cites this paper
• The IL-2 receptor complex: its structure, function, and target genes.

  1993cites this paper
• Biochemical properties of a novel 28KDA protein tyrosine kinase partially purified from the particulate fraction of rat spleen.

  1993cites this paper
• Interleukin-2 receptor signal transduction: translocation of active serine-threonine kinase Raf-1 from IL-2 receptor into cytosol depends on IL-2-induced tyrosine kinase activation.

  1993cites this paper
• IL-2 induces transient and specific decrease in cytosolic protein phosphatase PP1 activity in murine T cell lines.

  1993cites this paper
• Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction.

  1993cites this paper
• 3 - Identification of Intracellular Mediators of the Actions of Cytokines: Identifying Proteins Involved in Kinase Signaling Pathways

  1993cites this paper
• Effect of transforming growth factor-beta on early and late activation events in human T cells.

  1993cites this paper
• Interleukin 2 regulates Raf-1 kinase activity through a tyrosine phosphorylation-dependent mechanism in a T-cell line.

  1993cites this paper
• Signal transduction via phosphorylated adhesion molecule, LFA-1 beta (CD18), is increased by culture of natural killer cells with IL-2 in the generation of lymphokine-activated killer cells.

  1993cites this paper
• Reconstitution of functional interleukin 2 receptor complexes on fibroblastoid cells: involvement of the cytoplasmic domain of the gamma chain in two distinct signaling pathways.

  1993cites this paper
• The serine-rich cytoplasmic domain of the interleukin-2 receptor beta chain is essential for interleukin-2-dependent tyrosine protein kinase and phosphatidylinositol-3-kinase activation.

  1993cites this paper
• Mutation of Asp20 of human interleukin‐2 reveals a dual role of the p55 α chain of the interleukin‐2 receptor

  1993cites this paper
• Association of p56lck with IL‐2 receptor beta chain is critical for the IL‐2‐induced activation of p56lck.

  1993cites this paper
• Characterization of an interleukin-2 (IL-2)-induced tyrosine phosphorylated 116-kDa protein associated with the IL-2 receptor beta-subunit.

  1993cites this paper
• Interleukin-2 induces tyrosine phosphorylation of the vav proto-oncogene product in human T cells: lack of requirement for the tyrosine kinase lck.

  1993cites this paper
• The Role of Diacylglycerol Kinase Activation and Phosphatidate Accumulation in Interleukin-2-Dependent Lymphocyte Proliferation

  1993cites this paper
• CD26 induces T-cell proliferation by tyrosine protein phosphorylation.

  1992cites this paper
• Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R

  1992cites this paper
• Interleukin 2 and tumor necrosis factor alpha are complementary for proliferation of the hematopoietic stem cell line LyD9.

  1992cites this paper
• Interleukin‐1 induces protein tyrosine phosphorylation in T cells

  1992cites this paper
• The interleukin-2 receptors: insights into a complex signalling mechanism.

  1992cites this paper
• Neither the LCK nor the FYN kinases are obligatory for IL-2-mediated signal transduction in HTLV-I-infected human T cells.

  1992cites this paper
• IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression.

  1992cites this paper
• Cross‐linking of surface IgM or IgD causes differential biological effects in spite of overlap in tyrosine (de)phosphorylation profile

  1992cites this paper
• T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction.

  1992cites this paper
• Phorbol ester inhibits granulocyte-macrophage colony-stimulating factor binding and tyrosine phosphorylation.

  1992cites this paper
• Regulation of SRC-family protein tyrosine kinases by interleukins, IL-2, and IL-3.

  1992cites this paper
• The IL-2/IL-2 receptor system: involvement of a novel receptor subunit, gamma chain, in growth signal transduction.

  1992cites this paper
• Examination of B lymphoid cell lines for membrane immunoglobulin-stimulated tyrosine phosphorylation and src-family tyrosine kinase mRNA expression.

  1992cites this paper
• Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that is essential for functional IL-2 binding and signaling

  1992cites this paper
• Interleukin 4 inhibits IL-2-induced proliferation of a human T-leukemia cell line without interfering with p56-LCK kinase activation.

  1992cites this paper
• Interleukin‐2 signal transduction in human NK cells: multisite phosphorylation and activation of the tyrosine kinase p56/ck

  1992cites this paper
• Characterization of a tyrosine kinase activity associated with the high-affinity interleukin 2 receptor complex.

  1992cites this paper
• A role for protein tyrosine kinase activity in natural cytotoxicity as well as antibody-dependent cellular cytotoxicity. Effects of herbimycin A.

  1992cites this paper
• Gene transfer investigations of p56-LCK function in IL-2-dependent T-cell lines: implications for mechanisms of IL-2-signal transduction.

  1992cites this paper
• Regulation of hematopoietic cell function by protein tyrosine kinase-encoding oncogenes, a review.

  1992cites this paper