Cloning and Characterization of Novel CIS Family Genes

Masuhara, Masaaki; Sakamoto, Hiroshi; Matsumoto, Akira; Suzuki, Ryoko; Yasukawa, Hideo; Mitsui, Kiyofumi; Wakioka, Toru; Tanimura, Shyu; Sasaki, Atsuo T.; Misawa, Hiroyuki; Yokouchi, Masahiro; Ohtsubo, Motoaki; Yoshimura, Akihiko

doi:10.1006/bbrc.1997.7484

Cited by 243 publications

(222 citation statements)

References 23 publications

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“…[172][173][174][175][176][177][178][179][180][181][182] This family of genes has a conserved SH2 domain and SOCS box. [172][173][174][175][176][177][178][179][180][181][182] The SOCS box, the C-terminal 40 amino acids, is implicated in stability and degradation of the protein by targeting it to the proteosome. [175][176][177] CIS inhibits STAT5 activation by competing for its receptor-binding site.…”

Section: Overview Of Jak/stat Pathwaymentioning

confidence: 99%

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

et al. 2008

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Mutations and chromosomal translocations occur in leukemic cells that result in elevated expression or constitutive activation of various growth factor receptors and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are often activated by mutations in upstream genes. The Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak kinases and the phosphatase and tensin homologue deleted on chromosome 10 ( PTEN) phosphatase are also frequently mutated or their expression is altered in certain hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival pathways. Aberrant regulation of the survival pathways can contribute to uncontrolled cell growth and lead to leukemia. In this review, we describe the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize recent data regarding the regulation and mutation status of these pathways and their involvement in leukemia

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Section: Overview Of Jak/stat Pathwaymentioning

confidence: 99%

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

et al. 2008

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“…Two classes of molecules, Src homology 2 (SH2) 3 domain-containing protein tyrosine phosphatase and suppressor of cytokine signaling (SOCS), have been shown to inhibit IL-4-induced STAT6 phosphorylation in various cell types (23)(24)(25)(26). SH2-containing phosphatase (SHP-1) dephosphorylates STAT6 in B cells, macrophages, and fibroblast cells (27)(28)(29).…”

Section: T Helper Type 1 Cells Are Central Immune Components Inmentioning

confidence: 99%

IFN-γ Suppresses STAT6 Phosphorylation by Inhibiting Its Recruitment to the IL-4 Receptor

Huang

Xin

Coleman

et al. 2005

The Journal of Immunology

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Polarized Th1 cells show a stable phenotype: they become insensitive to IL-4 stimulation and lose the potential to produce IL-4. Previously, we reported that IFN-γ played a critical role in stabilizing Th1 phenotype. However, the mechanism by which IFN-γ stabilizes Th1 phenotype is not clear. In this study, we compared STAT6 phosphorylation in wild-type (WT) and IFN-γ receptor knockout (IFNGR−/−) Th1 cells. We found a striking diminution of STAT6 phosphorylation in differentiated WT Th1 cells, but not in differentiated IFNGR−/− Th1 cells. The impairment of STAT6 phosphorylation in differentiated WT Th1 cells was not due to a lack of IL-4R expression or phosphorylation. Jak1 and Jak3 expression and phosphorylation were comparable in both cell types. No differential expression of suppressor of cytokine signaling 1 (SOCS1), SOCS3, or SOCS5 was observed in the two cell types. In addition, Src homology 2-containing phosphatase mutation did not affect IL-4-induced STAT6 phosphorylation in differentiated Th1 cells derived from viable motheaten (mev/mev) mice. These results led us to focus on a novel mechanism. By using a pulldown assay, we observed that STAT6 in WT Th1 cells bound less effectively to the phosphorylated IL-4R/GST fusion protein than that in IFNGR−/− Th1 cells. Our results suggest that IFN-γ may suppress phosphorylation of STAT6 by inhibiting its recruitment to the IL-4R.

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“…Toward this end, we investigated the pathological events before AD onset using a mouse aortic stress model9 with macrophage‐specific knockout of Socs3 , a negative feedback factor in Stat3 signaling (mSOCS3‐KO mice) 10, 11. Here, we report a series of pathological events preceding AD onset in which macrophage Socs3 determines whether the aortic tissue adapts to stress or undergoes AD.…”

Section: Introductionmentioning

confidence: 99%

Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection

Ohno‐Urabe

Aoki

Nishihara

et al. 2018

JAHA

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BackgroundAortic dissection (AD) is a life‐threatening medical emergency caused by the abrupt destruction of the intimomedial layer of the aortic walls. Given that previous studies have reported the involvement of proinflammatory cytokine interleukin‐6 in AD pathogenesis, we investigated the role of signal transduction and activator of transcription 3 signaling, a downstream pathway of interleukin‐6 in macrophages in pathogenesis of AD.Methods and ResultsWe characterized the pathological and molecular events triggered by aortic stress, which can lead to AD. Aortic stress on the suprarenal aorta because of infrarenal aorta stiffening and angiotensin II infusion for 1 week caused focal medial rupture at the branching point of the celiac trunk and superior mesenteric artery. This focal medial rupture healed in 6 weeks in wild‐type (WT) mice, but progressed to AD in mice with macrophage‐specific deletion of Socs3 gene (mSocs3‐KO). mSocs3‐KO mice showed premature activation of cell proliferation, an inflammatory response, and skewed differentiation of macrophages toward the tissue‐destructive phenotype. Concomitantly, they showed aberrant phenotypic modulation of smooth muscle cells and transforming growth factor beta signaling, which are likely to participate in tissue repair. Human AD samples revealed signal transduction and activator of transcription 3 activation in adventitial macrophages adjacent to the site of tissue destruction.ConclusionsThese findings suggest that AD development is preceded by focal medial rupture, in which macrophage Socs3 maintains proper inflammatory response and differentiation of SMCs, thus promoting fibrotic healing to prevent tissue destruction and AD development. Understanding the sequence of the pathological and molecular events preceding AD development will help predict and prevent AD development and progression.

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Cloning and Characterization of Novel CIS Family Genes

Cited by 243 publications

References 23 publications

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to leukemia

IFN-γ Suppresses STAT6 Phosphorylation by Inhibiting Its Recruitment to the IL-4 Receptor

Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection

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