Therapeutic applications in the chemokine superfamily

Houshmand, Pantea; Zlotnik, Albert

doi:10.1016/s1367-5931(03)00086-3

Cited by 40 publications

(29 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tumor cells produce large amounts of chemokines in vitro and in vivo, and tumor-derived chemokines are responsible for the recruitment of tumor-infiltrating leukocytes that act in many instances as a source of tumor growth factors and angiogenic cytokines [2,3]. Likewise, the secretion of chemokines by surrounding stromal cells contributes to an extensive cross-talk, which may be beneficial or a hindrance for tumor cell progression.…”

Section: Introductionmentioning

confidence: 99%

Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma

et al. 2007

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma

et al. 2007

View full text Add to dashboard Cite

“…GPCRs play key roles in cellular signaling to regulate many important physiological processes, including cellular differentiation [2], immune response [3], smell [4], taste [5], vision [6], heart rate regulation [7], learning and memory [8], and energy homeostasis [9], [10]. They are stimulated by natural ligands, such as light, odorants, biogenic amines, lipids, and peptide hormones.…”

Section: Introductionmentioning

confidence: 99%

Engineering the Melanocortin-4 Receptor to Control Constitutive and Ligand-Mediated Gs Signaling In Vivo

et al. 2007

View full text Add to dashboard Cite

The molecular and functional diversity of G protein–coupled receptors is essential to many physiological processes. However, this diversity presents a significant challenge to understanding the G protein–mediated signaling events that underlie a specific physiological response. To increase our understanding of these processes, we sought to gain control of the timing and specificity of Gs signaling in vivo. We used naturally occurring human mutations to develop two Gs-coupled engineered receptors that respond solely to a synthetic ligand (RASSLs). Our Gs-coupled RASSLs are based on the melanocortin-4 receptor, a centrally expressed receptor that plays an important role in the regulation of body weight. These RASSLs are not activated by the endogenous hormone α-melanocyte-stimulating hormone but respond potently to a selective synthetic ligand, tetrahydroisoquinoline. The RASSL variants reported here differ in their intrinsic basal activities, allowing the separation of the effects of basal signaling from ligand-mediated activation of the Gs pathway in vivo. These RASSLs can be used to activate Gs signaling in any tissue, but would be particularly useful for analyzing downstream events that mediate body weight regulation in mice. Our study also demonstrates the use of human genetic variation for protein engineering.

show abstract

“…Three of these code for chemokines or cytokines (Cxcl10, Scya2, IL-6) potentially involved in the modulation of the immune response (Houshmand & Zlotnik 2003). Three others code for signaling proteins (Gbp2, C2ta, Irf1) that together with seven others previously mentioned in the Signal transduction category (Socs3, Jak2, Socs1, Stat1, Ptprn, Stat3, Cish) are known to mediate intracellular transduction of cytokines (Samuel 2001, Houshmand & Zlotnik 2003, van den Elsen et al 2004. Four genes are known to be involved in the regulation of antigen presentation to cytotoxic T cells, whose expression is typically IFN-dependent (Tap1, RT1Aw2, Lmp2, Psme2) (Marincola et al 2000(Marincola et al , 2003.…”

Section: Genes Involved In the Regulation Of The Immune Responsementioning

confidence: 99%

RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response

Puxeddu¹,

Knauf²,

Sartor³

et al. 2005

Endocrine-Related Cancer

View full text Add to dashboard Cite

RET/PTC rearrangements represent key genetic events involved in papillary thyroid carcinoma (PTC) initiation. The aim of the present study was to identify the early changes in gene expression induced by RET/PTC in thyroid cells. For this purpose, microarray analysis was conducted on PCCL3 cells conditionally expressing the RET/PTC3 oncogene. Gene expression profiling 48 h after activation of RET/PTC3 identified a statistically significant modification of expression of 270 genes. Quantitative PCR confirmation of 20 of these demonstrated 90% accuracy of the microarray. Functional clustering of genes with greater than or less than 1.75-fold expression change (86 genes) revealed RET/PTC3-induced regulation of genes with key functions in apoptosis (Ripk3, Tdga), cell-cell signaling (Cdh6, Fn1), cell cycle (Il24), immune and inflammation response (Cxcl10, Scya2, Il6, Gbp2, Oas1, Tap1, RT1Aw2, C2ta, Irf1, Lmp2, Psme2, Prkr), metabolism (Aldob, Ptges, Nd2, Gss, Gstt1), signal transduction (Socs3, Nf1, Jak2, Cpg21, Dusp6, Socs1, Stat1, Stat3, Cish) and transcription (Nr4a1, Junb, Hfh1, Runx1, Foxe1). Genes coding for proteins involved in the immune response and in intracellular signal transduction pathways activated by cytokines and chemokines were strongly represented, indicating a critical role of RET/PTC3 in the early modulation of the immune response.

show abstract

Therapeutic applications in the chemokine superfamily

Cited by 40 publications

References 27 publications

Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma

Profiles of chemokine receptors in melanocytic lesions: de novo expression of CXCR6 in melanoma

Engineering the Melanocortin-4 Receptor to Control Constitutive and Ligand-Mediated Gs Signaling In Vivo

RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response

Contact Info

Product

Resources

About