Interleukin 4 induces membrane Thy-1 expression on normal murine B cells.

Snapper, Clifford M.; Hornbeck, Peter; Atasoy, Ulus; Pereira, Geraldo M. B.; Paul, William E.

doi:10.1073/pnas.85.16.6107

Cited by 30 publications

(10 citation statements)

References 36 publications

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“…The biological function of Thy1 is poorly understood, but it may likely be involved in signal transduction from the plasma membrane, because it was shown that thymocytes of Thy1-deficient mice exhibit augmented TCR signaling and impaired T cell differenti-ation (30). Other studies showed that LPS+IL-4-stimulated B cells, but not LPS-stimulated B cells, upregulate Thy1 (31,32). We confirm and extend these findings by showing that STAT6 expression in B cells is required for this effect.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis

Mokada-Gopal

Boeser

Lehmann

et al. 2017

The Journal of Immunology

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The transcription factor STAT6 plays a key role in mediating signaling downstream of the receptors for IL-4 and IL-13. In B cells, STAT6 is required for class switch recombination to IgE and for germinal center formation during type 2 immune responses directed against allergens or helminths. In this study, we compared the transcriptomes and proteomes of primary mouse B cells from wild-type and STAT6-deficient mice cultured for 4 d in the presence or absence of IL-4. Microarray analysis revealed that 214 mRNAs were upregulated and 149 were downregulated >3-fold by IL-4 in a STAT6-dependent manner. Across all samples, ∼5000 proteins were identified by label-free quantitative liquid chromatography/mass spectrometry. A total of 149 proteins was found to be differentially expressed >3-fold between IL-4–stimulated wild-type and STAT6−/− B cells (75 upregulated and 74 downregulated). Comparative analysis of the proteome and transcriptome revealed that expression of these proteins was mainly regulated at the transcriptional level, which argues against a major role for posttranscriptional mechanisms that modulate the STAT6-dependent proteome. Nine proteins were selected for confirmation by flow cytometry or Western blot. We show that CD30, CD79b, SLP-76, DEC205, IL-5Rα, STAT5, and Thy1 are induced by IL-4 in a STAT6-dependent manner. In contrast, Syk and Fc receptor–like 1 were downregulated. This dataset provides a framework for further functional analysis of newly identified IL-4–regulated proteins in B cells that may contribute to germinal center formation and IgE switching in type 2 immunity.

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Section: Discussionmentioning

confidence: 99%

Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis

Mokada-Gopal

Boeser

Lehmann

et al. 2017

The Journal of Immunology

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“…It increases the expression of class II MHC molecules in B cells (18), enhances expression of CD23 (19), upregulates the expression of the IL-4 receptor (20), and, in association with lipopolysaccharide, allows B cells to express Thy 1 (21). It also acts as a co-mitogen for B cell growth (22).…”

Section: Introductionmentioning

confidence: 98%

THE IL-4 RECEPTOR: Signaling Mechanisms and Biologic Functions

Nelms

Keegan

Zamorano

et al. 1999

Annu. Rev. Immunol.

1,424

1,291

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Interleukin-4 is a multifunctional cytokine that plays a critical role in the regulation of immune responses. Its effects depend upon binding to and signaling through a receptor complex consisting of the IL-4R alpha chain and the common gamma chain (gamma c), resulting in a series of phosphorylation events mediated by receptor-associated kinases. In turn, these cause the recruitment of mediators of cell growth, of resistance to apoptosis, and of gene activation and differentiation. Here we describe our current understanding of the organization of the IL-4 receptor, of the signaling pathways that are induced as a result of receptor occupancy, and of the various mechanisms through which receptor function is modulated. We particularly emphasize the modular nature of the receptor and the specialization of different receptor regions for distinct functions, most notably the independent regulation of cell growth and gene activation.

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“…For example, IL-4 plays a central role in promoting the differentiation of Ag-stimulated naive T cells to develop into Th2 cells and is also responsible for the induction of B cell Ig class switching to IgE (1). In addition, IL-4 acts as a comitogen for T and B cell growth (2,3). Like other cytokines, IL-4 induces the activation of signal transduction pathways that are used to regulate cell growth and differentiation (4).…”

Section: Fes Mediates the Il-4 Activation Of Insulin Receptor Substramentioning

confidence: 99%

“…Because the basal activities of p70 S6K and Akt/PKB can be deprived in murine myeloid 32D/IRS-1 (2) cells under serum/IL-3 starvation, we generated 32D/IRS-1 stable transfectants expressing vector (control 3, 4), wild-type (Fes WT 3, 5), or kinase-inactive Fes (Fes KE 2,12,24) to study the activation of p70 S6K and Akt/PKB in response to IL-4. As has been previously shown (40,41), IL-4 can induce phosphorylation of Akt on Ser 473 (Fig.…”

Section: Kinase-inactive Fes Inhibits the Activation Of P70 S6k But Nmentioning

confidence: 99%

Fes Mediates the IL-4 Activation of Insulin Receptor Substrate-2 and Cellular Proliferation

Jiang

Foltenyi

Kashiwada

et al. 2001

The Journal of Immunology

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Although Jak kinases are essential for initiating cytokine signaling, the role of other nonreceptor tyrosine kinases in this process remains unclear. We have examined the role of Fes in IL-4 signaling. Examination of Jak1-deficient cell lines demonstrates that Jak1 is required for the activation of Fes by IL-4. Experiments studying signaling molecules activated by IL-4 receptor suggest that IL-4 signaling can be subdivided into Fes-dependent and Fes-independent pathways. Overexpression of kinase-inactive Fes blocks the IL-4 activation of insulin receptor substrate-2, but not STAT6. Fes appears to be a downstream kinase from Jak1/Jak3 in this process. Further examination of downstream signaling demonstrates that kinase-inactive Fes inhibits the recruitment of phosphoinositide 3-kinase to the activated IL-4 receptor complex and decreases the activation of p70S6k kinase in response to IL-4. This inhibition correlates with a decrease in IL-4-induced proliferation. In contrast, mutant Fes does not inhibit the activation of Akt by IL-4. These data demonstrate that signaling pathways activated by IL-4 require different tyrosine kinases. This differential requirement predicts that specific kinase inhibitors may permit the disruption of specific IL-4-induced functions.

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Interleukin 4 induces membrane Thy-1 expression on normal murine B cells.

Cited by 30 publications

References 36 publications

Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis

Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis

THE IL-4 RECEPTOR: Signaling Mechanisms and Biologic Functions

Fes Mediates the IL-4 Activation of Insulin Receptor Substrate-2 and Cellular Proliferation

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