SHP-2 Regulates SOCS-1-mediated Janus Kinase-2 Ubiquitination/Degradation Downstream of the Prolactin Receptor

Ali, Samir; Nouhi, Zaynab; Chughtai, Naila; Ali, Suhad

doi:10.1074/jbc.m306758200

Cited by 74 publications

(56 citation statements)

References 38 publications

(35 reference statements)

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“…Inhibition of EGF signaling was shown to depend on the SOCS-5 SOCS box and most likely results from enhanced receptor degradation over time. There is now compelling evidence that the SOCS box recruits E3 ubiquitin ligase activity and, in the case of SOCS-1, results in polyubiquitination of VAV, JAK2, and FAK and a decrease in the half-life of those proteins (36)(37)(38)(39). Our data provide evidence of SOCS box-dependent degradation of a receptor protein, the EGF-R.…”

Section: Discussionmentioning

confidence: 55%

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling

Nicholson

Metcalf

Sprigg

et al. 2005

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

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The suppressors of cytokine signaling (SOCS) proteins are a family of SH2 domain-containing intracellular inhibitors of cytokine signal transduction that act by several different mechanisms. Recent evidence suggests that the action of the SOCS proteins may extend beyond the cytokine receptors to signaling initiated by members of the tyrosine kinase receptor family. In this study, the ability of SOCS-5 to negatively regulate signaling cascades downstream of the epidermal growth factor receptor (EGF-R) has been examined by using an EGF-responsive cell line engineered to constitutively express the EGF-R and SOCS-5 or SOCS-5 mutants. SOCS-5 associated with the EGF-R complex in an EGF-independent manner, and the mitogenic response to EGF of all SOCS-5-expressing cell lines was dramatically inhibited when compared with control cell lines. Furthermore, this effect was abrogated after deletion of the SOCS-5 SOCS box. This result suggests that the inhibition of signaling occurs through enhanced proteasomal degradation of the EGF-R through SOCS box recruitment of E3 ubiquitin ligase activity.

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Section: Discussionmentioning

confidence: 55%

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling

Nicholson

Metcalf

Sprigg

et al. 2005

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

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“…37 Another possibility, given that HDACi have been demonstrated to hyperacetylate a number of proteins other than histones, The HDAC inhibitor ITF2357 downmodulates JAK2 V617F V Guerini et al including tubulin, p53 and BCL-6, 38,39 is that ITF2357 may induce hyperacetylation of JAK2 itself or of another protein involved in its stabilization, such as SOCS1. 8,40 All these different hypotheses are currently under investigation and are beyond the scope of this report. Interestingly, the effect of ITF2357 on colony growth is similar to that observed using the EGFR inhibitor Erlotinib, which also allowed preferential growth of JAK2 V617F -negative cells in colony assays.…”

Section: Discussionmentioning

confidence: 99%

The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2V617F

et al. 2007

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We investigated the activity of ITF2357, a novel histone deacetylase inhibitor (HDACi) with antitumor activity, on cells carrying the JAK2 V617F mutation obtained from polycythemia vera (PV) and essential thrombocythemia (ET) patients as well as the HEL cell line. The clonogenic activity of JAK2 V617F mutated cells was inhibited by low concentrations of ITF2357 (IC 50 0.001-0.01 lM), 100-to 250-fold lower than required to inhibit growth of normal or tumor cells lacking this mutation. Under these conditions, ITF2357 allowed a seven fold increase in the outgrowth of unmutated over mutated colonies. By western blotting we showed that in HEL cells, ITF2357 led to the disappearance of total and phosphorylated JAK2 V617F as well as pSTAT5 and pSTAT3, but it did not affect the wild-type JAK2 or STAT proteins in the control K562 cell line. By real-time PCR, we showed that, upon exposure to ITF2357, JAK2 V617F mRNA was not modified in granulocytes from PV patients while the expression of the PRV-1 gene, a known target of JAK2, was rapidly downmodulated. Altogether, the data presented suggest that ITF2357 inhibits proliferation of cells bearing the JAK2 V617F mutation through a specific downmodulation of the JAK2 V617F protein and inhibition of its downstream signaling.

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“…4B). Because tyrosine-phosphorylated Dab1 activates Src kinases in a feed-forward fashion (3), two interpretations of this result are possible: 1) the activation of Src kinases or downstream targets is required for the activation of the ubiquitin-proteasome system, for example, by phosphorylation of the ubiquitin ligase; or 2) tyrosine phosphorylation of Dab1 itself provides a recognition signal for the ubiquitination machinery, similar to the prolactin-dependent tyrosine phosphorylation, ubiquitination, and degradation of Janus kinase-2 (42).…”

Section: Fig 1 Reelin Regulates the Protein Levels Of Dab1 In Neuronsmentioning

confidence: 99%

Apolipoprotein E Receptors Are Required for Reelin-induced Proteasomal Degradation of the Neuronal Adaptor Protein Disabled-1

Bock

Jossin

May

et al. 2004

Journal of Biological Chemistry

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Dab1 consists of an aminoterminal phosphotyrosine binding domain followed by a stretch of tyrosyl residues and a large carboxyl-terminal domain. At least two of the tyrosine residues are phosphorylated in vivo by the Src family kinase Fyn (2, 3) in response to Reelin. Tyrosine phosphorylation of Dab1 at these residues is essential for the transduction of the Reelin signal (4) and requires binding of Reelin to its receptors, apolipoprotein E receptor 2 (apoER2) and VLDL receptor, two members of the low density lipoprotein (LDL) receptor gene family (reviewed in Ref. 5). Tyrosinephosphorylated Dab1 triggers the activation of class I phosphatidylinositol 3 (PI3)-kinase (6, 7), which has been shown to be necessary for the formation of a normal cortical plate (8).The conserved phosphotyrosine binding domain mediates the interaction of Dab1 with unphosphorylated NPXY tetraamino acid sequences in the cytosolic domains of transmembrane receptors, including members of the LDL receptor family (9, 10), and with phosphoinositides at the inner leaflet of the plasma membrane (10 -12). The function of the carboxyl-terminal sequence is less well defined. It is not required for the tyrosine phosphorylation of Dab1 or the activation of Src family kinases and PI3-kinase by Reelin (7). Mice expressing a carboxyl-terminal truncated Dab1 protein (p45) display normal brain development (13), although haploinsufficiency of the p45 allele causes a restricted phenotype characterized by positioning defects of late-born cortical plate neurons and hippocampal CA1 pyramidal cells. Interestingly, a serine residue near the carboxyl terminus of Dab1 is phosphorylated by Cdk5 in vivo (14), a proline-directed serine/threonine kinase, which is also essential for the correct positioning of postmitotic neurons (reviewed in Ref. 15), but the functional significance of this biochemical cross-talk remains unclear.How the Reelin signal in migrating neurons is terminated is not known. The Reelin-induced tyrosine phosphorylation of Dab1 declines only after prolonged incubation periods (16). Treatment of neurons with sodium orthovanadate did not significantly increase Dab1 tyrosine phosphorylation, suggesting that phosphotyrosine phosphatases do not play a major role in limiting the response to Reelin (16). Up-regulation of Dab1 protein levels is a common feature in mice carrying dysfunctional mutations of genes that encode key Reelin signaling molecules, namely Reelin itself (17), its receptors apoER2 and VLDLR (18), and its kinase Fyn (2, 3), as well as in mice that * This work was supported in part by National Institutes of Health Grants HL20948, HL63762, and NS43408, the Alzheimer's Association, the Wolfgang-Paul Award of the Humboldt Foundation, the Perot Family Foundation (to J. H.), and an Emmy Noether fellowship of the Deutsche Forschungsgemeinschaft (to P. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Secti...

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SHP-2 Regulates SOCS-1-mediated Janus Kinase-2 Ubiquitination/Degradation Downstream of the Prolactin Receptor

Cited by 74 publications

References 38 publications

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling

Suppressor of cytokine signaling (SOCS)-5 is a potential negative regulator of epidermal growth factor signaling

The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2V617F

Apolipoprotein E Receptors Are Required for Reelin-induced Proteasomal Degradation of the Neuronal Adaptor Protein Disabled-1

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