Insulin Induction of SOCS-2 and SOCS-3 mRNA Expression in C2C12 Skeletal Muscle Cells Is Mediated by Stat5*

Sadowski, Cynthia L.; Choi, Tae-Soon; Le, Maithao; Wheeler, Thomas T.; Wang, Lu‐Hai; Sadowski, Henry B.

doi:10.1074/jbc.m101014200

Cited by 63 publications

(50 citation statements)

References 47 publications

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“…Treatment with human rG-CSF resulted in a dramatic increase of SOCS-3 mRNA within 45 min. This rapid induction of SOCS-3 was similar to that observed with other cytokines (47)(48)(49) and this indicates that SOCS-3 is an immediate early gene induced by G-CSF to rapidly modulate G-CSFR-mediated signaling. The strong and rapid induction of SOCS-3 mRNA in myeloid cells by G-CSF reported in this study, together with the previously reported potent induction of SOCS-3 by G-CSF, GM-CSF, and IL-3 in bone marrow cells (22), is a strong indication for SOCS-3 being an important regulator of signal transduction in immune cells.…”

Section: Discussionsupporting

confidence: 82%

Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction

Hörtner

Nielsch

Mayr

et al. 2002

The Journal of Immunology

122

101

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G-CSF is a polypeptide growth factor used in treatment following chemotherapy. G-CSF regulates granulopoiesis and acts on its target cells by inducing homodimerization of the G-CSFR, thereby activating intracellular signaling cascades. The G-CSFR encompasses four tyrosine motifs on its cytoplasmic tail that have been shown to recruit a number of regulatory proteins. Suppressor of cytokine signaling 3 (SOCS-3), also referred to as cytokine-inducible Src homolgy 2-containing protein 3, is a member of a recently discovered family of feedback inhibitors that have been shown to inhibit the Janus kinase/STAT pathway. In this study, we demonstrate that human SOCS-3 is rapidly induced by G-CSF in polymorphonuclear neutrophils as well as in the myeloid precursor cell line U937 and that SOCS-3 negatively regulates G-CSFR-mediated STAT activation. Most importantly, we show that SOCS-3 is recruited to the G-CSFR in a phosphorylation-dependent manner and we identify phosphotyrosine (pY)729 as the major recruitment site for SOCS-3. Furthermore, we demonstrate that SOCS-3 directly binds to this pY motif. Surface plasmon resonance analysis reveals a dissociation constant (KD) for this interaction of around 2.8 μM. These findings strongly suggest that the recruitment of SOCS-3 to pY729 is important for the modulation of G-CSFR-mediated signal transduction by SOCS-3.

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Section: Discussionsupporting

confidence: 82%

Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction

Hörtner

Nielsch

Mayr

et al. 2002

The Journal of Immunology

122

101

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“…Recent studies have implicated a role for IRS-1 as a negative regulator of differentiation (Wang et al, 1993;Kim et al, 1998;Sadowski et al, 2001). Activated IRS-1 is a frequent event associated with different kind of human tumors (breast cancer, leiomyomas, Wilms' tumors, rhabdomyosarcomas, liposarcomas, and adrenal cortical carcinomas; Chang et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Our novel findings are summarized as follows: (1) IRS-1 is expressed and activated in self-renewing ES cells; (2) IRS-1 protein expression levels are down-regulated upon LIF withdrawal and induction of ES cell differentiation; (3) LIF induces tyrosine phosphorylation of IRS-1 in self-renewing ES cells; (4) Reduction of IRS-1 expression by siRNA causes differentiation of ES cells even in the presence of LIF, down-regulating Oct4 protein expression and AP activity; (5) Targeting of IRS-1 impairs the capacity of LIF to induce PI3K dependent signals, resulting in a decrease of AKT and GSK-3b phosphorylation; (6) IRS-1 targeting results also in the down regulation of both Id1 and Id2 proteins expression; (7) Although there is a substantial literature on the role of IRS-1 in cell proliferation and differentiation (Wang et al, 1993;Kim et al, 1998;Shima et al, 1998;Bohni et al, 1999;Valentinis et al, 2000;Brogiolo et al, 2001;Sadowski et al, 2001), information on its functions in ES cells is lacking. In the current study we show that the presence and activation of IRS-1 is critical for LIF mediated self-renewal of ES cells.…”

Section: Discussionmentioning

confidence: 99%

Insulin receptor substrate (IRS)‐1 regulates murine embryonic stem (mES) cells self‐renewal

Rubin

Arzumanyan

Soliera

et al. 2007

Journal Cellular Physiology

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Mouse embryonic stem (mES) cells are pluripotent cells that can be propagated in vitro with leukemia inhibitory factor (LIF) and serum. Intracellular signaling by LIF is principally mediated by activation of STAT-3, although additional pathways for self-renewal have been described. Here, we identified a novel role for Insulin receptor substrate-1 (IRS-1) as a critical factor in mES cells self-renewal and differentiation. IRS-1 is expressed and tyrosyl phosphorylated during mES cells self-renewal. Differentiation of mES cells, by LIF withdrawal, is associated with a marked reduction in IRS-1 expression. Targeting of IRS-1 by si-IRS-1 results in a severe reduction of Oct-4 protein expression and alkaline phosphatase activity, markers of undifferentiated mES cells. IRS-1 targeting does not interfere with LIF-induced STAT-3 phosphorylation, but negatively affects protein kinase B (PKB/AKT) and glycogen synthase kinase-3 (GSK-3b) phosphorylation, which are downstream effectors of the LIF-mediated PI3K signaling cascade. Targeting of IRS-1 also results in a marked down regulation of Id-1 and Id-2 proteins expression, which are important components for self-renewal of ES cells. Conversely, over expression of IRS-1 inhibits mES cell differentiation. Taken together, these results suggest that expression and activity of IRS-1 are critical to the maintenance of the self-renewal program in mES cells.

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“…Both insulin and Ang II are individually able to induce the expression of SOCS proteins in tissues of living animals and in cultivated cell-lines [68][69][70][71][72]. Depending on the tissue or cell line studied, insulin is able to induce the expression of SOCS-2 [69] and/or SOCS-3 [68,73] through the activation of STAT-5b.…”

Section: The Late Events Affected By the Insulin-ang II Cross-talkmentioning

confidence: 99%

“…Depending on the tissue or cell line studied, insulin is able to induce the expression of SOCS-2 [69] and/or SOCS-3 [68,73] through the activation of STAT-5b. Once induced, SOCS-3 can bind to the Tyr 960 of the IR and hamper its capacity to induce the tyrosine phosphorylation of STAT5b, IRS-1 and IRS-2 [68,70,74].…”

Section: The Late Events Affected By the Insulin-ang II Cross-talkmentioning

confidence: 99%

The multi‐faceted cross‐talk between the insulin and angiotensin II signaling systems

Velloso

Folli

Perego

et al. 2006

Diabetes Metabolism Res

103

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SummaryInsulin and angiotensin II are hormones that play pivotal roles in the control of two vital and closely related systems, the metabolic and the circulatory systems, respectively. A failure in the proper action of each of these hormones results, to a variable degree, in the development of two highly prevalent and commonly overlapping diseases -diabetes mellitus and hypertension. In recent years, a series of studies has revealed a tight connection between the signal transduction pathways that mediate insulin and angiotensin II actions in target tissues. This molecular cross-talk occurs at multiple levels and plays an important role in phenomena that range from the action of anti-hypertensive drugs to cardiac hypertrophy and energy acquisition by the heart. At the extracellular level, the angiotensin-converting enzyme controls angiotensin II synthesis but also interferes with insulin signaling through the proper regulation of angiotensin II and through the accumulation of bradykinin. At an early intracellular level, angiotensin II, acting through JAK-2/IRS-1/PI3-kinase, JNK and ERK, may induce the serine phosphorylation and inhibition of key elements of the insulin-signaling pathway. Finally, by inducing the expression of the regulatory protein SOCS-3, angiotensin II may impose a late control on the insulin signal. This review will focus on the main advances obtained in this field and will discuss the implications of this molecular cross-talk in the common clinical association between diabetes mellitus and hypertension.

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Insulin Induction of SOCS-2 and SOCS-3 mRNA Expression in C2C12 Skeletal Muscle Cells Is Mediated by Stat5*

Cited by 63 publications

References 47 publications

Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction

Suppressor of Cytokine Signaling-3 Is Recruited to the Activated Granulocyte-Colony Stimulating Factor Receptor and Modulates its Signal Transduction

Insulin receptor substrate (IRS)‐1 regulates murine embryonic stem (mES) cells self‐renewal

The multi‐faceted cross‐talk between the insulin and angiotensin II signaling systems

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