CXCR4 Membrane Protein Introduction

Introduction of CXCR4

CXCR4 is a G protein-coupled receptor in the CXC chemokine receptor family, encoded by CXCR4 gene. It is one of seven CXC chemokine receptors (CXCR1-CXCR7) in mammals. The receptors can recognize CXC chemokine that possesses an E-L-R amino acid motif. CXCR4 is widely expressed in many human tissues, such as lymph node, bone marrow. Recently, most studies focus on the role of CXCR4 in the pathological process of cancer.

Function of CXCR4 Membrane Protein

CXCR4 binds to its ligands, C-X-C chemokine CXCL12/SDF-1, leading to the activation of G protein-dependent signaling pathways. It is involved in a number of biological processes, such as organogenesis, hematopoiesis, and immune response. The previous studies showed that CXCR4 plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Besides, CXCR4 also plays a key role in the progression of cancer through activating several signal pathways, such as SAPK/JNK, MAPK, and ERK1/2. These pathways mediate tumor cells proliferation, survival, and migration. And the expression of CXCR4 has been detected highly in 23 different cancers of various origins while low or scantily in many healthy tissues. Low expression of CXCR4 can decrease cell growth, promote cell apoptosis. Additionally, CXCR4 acts as a coreceptor for HIV-1 regulating HIV infection.

Fig.1 Signal Transduction Pathways and Regulation of CXCR4. (Busillo, 2007)

Application of CXCR4 Membrane Protein in Literature

1. Berning P., et al. The CXCR4 antagonist plerixafor (AMD3100) promotes proliferation of Ewing sarcoma cell lines in vitro and activates receptor tyrosine kinase signaling. Cell Communication and Signaling. 2018, 16(1): 21. PubMed ID: 29776413
   
   

   The in vitro study shows that CXCR4 antagonist plerixafor can increase Ewing sarcoma cells viability and proliferation and promote cells chemotactic migration toward to plerixafor. And proliferative plerixafor responses are involved in the activation of multiple receptor tyrosine kinases. A multi-kinase inhibitor of both PDGFRB and the CXCR4 downstream kinase SRC can reduce this activation in some cell lines. These suggest that PDGFRB can act as a potential therapeutic co-target for CXCR4 in Ewing sarcoma.

2. Lapa C., et al. Feasibility of CXCR4-directed radioligand therapy in advanced diffuse large B cell lymphoma. Journal of Nuclear Medicine. 2018. PubMed ID: 29777009
   
   

   The study identifies that CXCR4-directed radioligand therapy (in combination with additional radioligand therapy) is feasible before allogeneic stem cell transplantation in diffuse large B cell lymphoma.

3. González-Arriagada W A., et al. Clinicopathologic significance of chemokine receptor (CCR1, CCR3, CCR4, CCR5, CCR7 and CXCR4) expression in head and neck squamous cell carcinomas. Journal of Oral Pathology & Medicine. 2018, 47(8): 755-763. PubMed ID: 29797610
   
   

   The finding shows that chemokine receptors may play an essential role in the progression of head and neck squamous cell carcinoma as well as the metastasis and recurrence of the regional lymph node. Low CXCR4 levels are significantly associated with both disease-specific and disease-free survival.

4. Zhang T., et al. High expression of CXCR4 and stem cell markers in a monocrotaline and chronic hypoxia-induced rat model of pulmonary arterial hypertension. Experimental & Therapeutic Medicine. 2018, 15(6): 4615-4622. PubMed ID: 29805477
   
   

   The study indicates that the high CXCR4 levels are observed in pulmonary arterial hypertension groups compared to controls, suggesting that CXCR4 associated with the pathogenesis of pulmonary arterial hypertension. Besides stem cells may play an important role in pulmonary vascular remodeling.

5. Wang X., et al. Effect of CXCR4 silencing with shRNA on MAPK signaling in ovarian cancer. Oncology Letter. 2018, 15(6): 10026-10030. PubMed ID: 29805693
   
   

   The study shows that silencing the CXCR4 gene with shRNA in SW626 ovarian cancer cells can increased apoptosis signal-regulating kinase 1 (ASK1) mRNA expression and phosphorylated-c-Jun protein expression, decrease extracellular-signal-regulated kinase (ERK1/2) protein expression, with a significance. At all, silencing the CXCR4 gene with shRNA can reduce cell proliferation, promote cell apoptosis, possibly regulated by MAPK signaling pathway.

CXCR4 Preparation Options

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Reference

1. Busillo J M and Benovic J L. (2007). Regulation of CXCR4 Signaling. Biochimica et Biophysica Acta. 1768(4), 952-63.

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