IL-4 Signaling Is Regulated through the Recruitment of Phosphatases, Kinases, and SOCS Proteins to the Receptor Complex

Losman, Julie A.; Chen, X. P.; Jiang, Haiming; Pan, Ping-Ying; Kashiwada, Masaki; Giallourakis, Cosmas; Cowan, Simone; Foltenyi, K.; Rothman, Paul B.

doi:10.1101/sqb.1999.64.405

Cited by 20 publications

(9 citation statements)

References 97 publications

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“…IL-4 acts through activation of the Jak/STAT signaling pathway and inhibits release of proinflammatory cytokines by monocytes. [44][45][46][47] Our data demonstrate that IL-4 also rapidly down-regulates the expression of mRNA for PAR1, PAR2, and PAR3 accompanied by a decrease in the cell surface expression of these receptors. The latter may somewhat precede that of mRNA, suggesting that regulation at the level of translation also may be involved.…”

Section: Discussionmentioning

confidence: 99%

Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells

Colognato

Slupsky

Jendrach

et al. 2003

Blood

213

215

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Section: Discussionmentioning

confidence: 99%

Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells

Colognato

Slupsky

Jendrach

et al. 2003

Blood

213

215

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“…Because STAT6 is the substrate for JAK1 and JAK3 in the JAK/STAT signaling pathway, and IL-4-induced STAT6 phosphorylation is mediated via activation of JAK1 and JAK3 (42), it was predictable that IL-4-induced STAT6 phosphorylation would be inhibited by the JAK phosphatase activity of CD45 (35, 39). Indeed, IL-4-induced STAT6 phosphorylation (Fig.…”

Section: Il-4-induced Jak1 Jak3 and Stat6 Phosphorylation Is Inhibimentioning

confidence: 99%

Human Activation-Induced Cytidine Deaminase Is Induced by IL-4 and Negatively Regulated by CD45: Implication of CD45 as a Janus Kinase Phosphatase in Antibody Diversification

Zhou

Saxon

Zhang

2003

The Journal of Immunology

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Activation-induced cytidine deaminase (AID) plays critical roles in Ig class switch recombination and VH gene somatic hypermutation. We investigated the role of IL-4 in AID mRNA induction, the signaling transduction involved in IL-4-mediated AID induction, and the effect of CD45 on IL-4-dependent AID expression in human B cells. IL-4 was able to induce AID expression in human primary B cells and B cell lines, and IL-4-induced AID expression was further enhanced by CD40 signaling. IL-4-dependent AID induction was inhibited by a dominant-negative STAT6, indicating that IL-4 induced AID expression via the Janus kinase (JAK)/STAT6 signaling pathway. Moreover, triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations. Thus, in humans, IL-4 alone is sufficient to drive AID expression, and CD40 signaling is required for optimal AID production; IL-4-induced AID expression is mediated via the JAK/STAT signaling pathway, and can be negatively regulated by the JAK phosphatase activity of CD45. This study indicates that the JAK phosphatase activity of CD45 can be induced by anti-CD45 Ab treatment, and this principle may find clinical application in modulation of JAK activation in immune-mediated diseases.

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“…STAT3 and STAT5 directly bind to the Pim-1 promoter at the gamma interferon activation sequences (ISFR/GAS) that upregulates Pim-1 gene expression [26][27][28][29]. Pim-1 protein can negatively regulate the JAK/STAT pathways by binding to a group of the SOCS proteins [30,31]. Furthermore, STATs are also regulated by a number of other factors such as p53, Pias3, Gfi1, NFκB and BCR-ABL ( Figure 2).…”

Section: P Im1 Y Q V G P L L G S G G F G S V Y S G I R V S D N L P V mentioning

confidence: 99%

Targeting Pim Kinases for Cancer Treatment: Opportunities and Challenges

Kumarasiri

Adams

et al. 2015

Future Med. Chem.

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Pim oncogenes are highly expressed in many types of hematological and solid cancers. Pim kinases regulate the network of signaling pathways that are critical for tumorigenesis and development, making Pim kinases the attractive drug targets. Currently, two approaches have been employed in designing Pim kinase inhibitors: ATP-mimetics and non-ATP mimetics; but all target the ATP-binding pocket and are ATP-competitive. In this review, we summarize the current progress in understanding the Pim-related structure and biology, and provide insights into the binding modes of some prototypical Pim-1 inhibitors. The challenges as well as opportunities are highlighted for development of Pim kinase inhibitors as potential anticancer agents.

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IL-4 Signaling Is Regulated through the Recruitment of Phosphatases, Kinases, and SOCS Proteins to the Receptor Complex

Cited by 20 publications

References 97 publications

Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells

Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells

Human Activation-Induced Cytidine Deaminase Is Induced by IL-4 and Negatively Regulated by CD45: Implication of CD45 as a Janus Kinase Phosphatase in Antibody Diversification

Targeting Pim Kinases for Cancer Treatment: Opportunities and Challenges

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