Differential effects of interleukin-2 and interleukin-4 on protein tyrosine phosphorylation in factor-dependent murine T cells

Augustine, James A.; Schlager, Janis W.; Abraham, Robert T.

doi:10.1016/0167-4889(90)90227-5

Cited by 40 publications

(20 citation statements)

References 46 publications

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“…Moreover, the phosphopeptide patterns generated by V8 digestion of the 170-kDa proteins were identical to each other. Thus (28)(29)(30)(31)(32)(33). However, no substrate in the 170-kDa size range was described in any of these studies.…”

Section: Discussionmentioning

confidence: 91%

Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

Wang

Keegan

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

159

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Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These rmdings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (it) insulin and IGF

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Section: Discussionmentioning

confidence: 91%

Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

Wang

Keegan

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

159

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“…IL-4 specifically induces tyrosine phosphorylation of its receptor and other intracellular substrates in lymphoid and hematopoietic cell lines of both murine and human origin (43)(44)(45). IL-4 signaling in many of these cells has been shown to involve tyrosine phosphorylation and/or receptor association of a number of downstream mediators including the Janus family tyrosine kinases, JAK1 and JAK3 (30,46,47) phosphatidyl inositol 3-kinase (43,48), or insulin receptor substrate-1 (48,49).…”

Section: Resultsmentioning

confidence: 99%

IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain.

Palmer-Crocker

Hughes²,

Pober³

1996

J. Clin. Invest.

101

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1 and markedly augments VCAM-1 expression induced by TNF or IL-1 (1-6). These changes favor the binding of eosinophils and T cells to endothelial cells (ECs). In addition, IL-4-treated ECs secrete the chemokine MCP-1 (7) and selectively stimulate transendothelial migration of eosinophils in vitro (8). The effects of IL-4 on EC differ from those on hematopoietic cell types in that IL-4 is not an endothelial mitogen or survival factor.IL-13 is another pleiotropic immunoregulatory cytokine (9, 10) that shares a number of biological properties with IL-4 (11-16). IL-13, like IL-4, selectively induces VCAM-1 in cultured human ECs (17, 18). IL-13 has been shown recently to stimulate tyrosine phosphorylation of the IL-4-binding subunit of the 140-kD IL-4 receptor (IL-4R) in a number of hematopoietic cell types (19), suggesting that IL-4 and IL-13 may activate a common tyrosine kinase. Two recent findings further suggest that the IL-13-binding subunit of the IL-13 receptor (IL-13R) may share at least one subunit with the IL-4R: ( a ) the IL-4 mutant protein Y124D, which inhibits IL-4-dependent reactions (20) also inhibits effects of IL-13 (21, 22); and ( b ) IL-13 competes with radiolabeled IL-4 for binding to some cells (21-24).The IL-2 receptor (IL-2R) ␥ chain is a functional component of the IL-4R in lymphocytes, required for tyrosine phosphorylation of the insulin receptor substrate-1 in response to IL-4 (25) and for IL-4-induced cell proliferation (26). The (IL-2R) ␥ chain, recently renamed the common ␥ chain ( ␥ c chain), is also a common receptor component of many other members of the cytokine receptor superfamily including , [30][31][32]34). It is not known if IL-13 can signal through ␥ c , but some cell lines of hematopoietic origin are known to respond to IL-4 and IL-13 in the absence of ␥ c (24,35). This evidence suggests two distinct signaling pathways for IL-4, one involving ␥ c , and an alternate pathway, shared with IL-13, that does not use ␥ c .Previous work by our laboratory has shown that IL-4 activates a protein tyrosine kinase that phosphorylates the IL-4R binding subunit in cultured human ECs and that activation of this protein tyrosine kinase may play a part in the signaling pathway leading to increased VCAM-1 expression in response to . We now show that IL-13, like IL-4, causes the activation of a protein tyrosine kinase in ECs that phosphorylates IL-4R, that both cytokines activate JAK2 and the Stat6 transcription factor, and that these responses cannot involve ␥ c , since this protein is not expressed in ECs. MethodsCell isolation and culture. ECs were isolated and cultured as described previously (37,38). ECs used in these experiments were of passage levels 2 to 5 and were free of detectable CD45 ϩ leukocytes. PHA- 1. Abbreviations used in this paper: EC, endothelial cell; JAK, Janus kinase; RT, reverse transcription; Stat, signal transducer and activator of transcription; VCAM-1, vascular cell adhesion molecule-1.

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“…The anti-CD16 3G8 hybridoma (21) was generously provided by D. M. Segal, National Cancer Institute/National Institutes of Health, Bethesda, MD. The anti-phosphotyrosine antibody-secreting hybridoma 1G2 was a gift from A. R. Frackelton, Jr. (Brown University, Providence, RI) and 1G2 monoclonal antibody (mAb) purification has been described (22). Affinity-purified polyclonal anti-phosphotyrosine antibodies were isolated from rabbit antisera raised against the v-abl-encoded tyrosine kinase (23,24 (23), precleared with bovine serum albumin-Sepharose, and then incubated with lG2-Sepharose for 3 h at 40C.…”

mentioning

confidence: 99%

“…NK cells were resuspended in 1-ml aliquots at 7 x 106 cells per ml. Cells were stimulated, reactions were terminated, and cell lysate extracts were prepared (22). Phosphotyrosyl proteins in the cell lysate extract were immunoprecipitated with 1G2-Sepharose for 3 h at 40C.…”

mentioning

confidence: 99%

Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function.

Einspahr

Abraham

Binstadt

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Differential effects of interleukin-2 and interleukin-4 on protein tyrosine phosphorylation in factor-dependent murine T cells

Cited by 40 publications

References 46 publications

Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the gamma c chain.

Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function.

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