| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Divisions of
* Infectious Diseases,
Experimental Pathology,
Pulmonary and Critical Care, and
Department of Immunology, Mayo Clinic, Rochester, MN 55905
Chemokine receptors are essential for triggering chemotaxis to
immune cells; however, a number of them can also mediate death when
engaged by nonchemokine ligands. When the chemokine receptor CXCR4 is
engaged by stromal cell-derived factor (SDF1)
, it triggers cells to
chemotax, and in some cell types such as neurons, causes cell death. To
elucidate this dual and opposing receptor function, we have
investigated whether CXCR4 activation by its chemokine SDF1 could
lead to the simultaneous activation of both anti- and proapoptotic
signaling pathways; the balance ultimately influencing cell survival.
CXCR4 activation in CD4 T cells by SDF1 led to the activation of the
prosurvival second messengers, Akt and extracellular signal-regulated
protein kinase. Selective inhibition of each signal demonstrated
that extracellular signal-regulated protein kinase is essential for
mediating SDF1-triggered chemotaxis but does not confer an
antiapoptotic state. In contrast, Akt activation through CXCR4 by
SDF1 interactions is necessary to confer resistance to apoptosis.
The proapoptotic signaling pathway triggered by SDF1-CXCR4
interaction involves the Gi protein-independent
activation of the proapoptotic MAPK (p38). Furthermore, other
chemokines and chemokine receptors also signal chemotaxis and
proapoptotic effects via similar pathways. Thus, Gi
protein-coupled chemokine receptors can function as death prone
receptors and the balance between the above signaling pathways will
ultimately mandate the fate of the activated
cell.
This article has been cited by other articles:
|
|
 |
|
  A. Saxena, J. E. Fish, M. D. White, S. Yu, J. W.P. Smyth, R. M. Shaw, J. M. DiMaio, and D. Srivastava Stromal Cell-Derived Factor-1{alpha} Is Cardioprotective After Myocardial Infarction Circulation, April 29, 2008; 117(17): 2224 - 2231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Diaz-Guerra, R. Vernal, M. J. del Prete, A. Silva, and J. A. Garcia-Sanz CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells J. Immunol., December 1, 2007; 179(11): 7352 - 7357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Hirbe, J. Rubin, O. Uluckan, E. A. Morgan, M. C. Eagleton, J. L. Prior, D. Piwnica-Worms, and K. N. Weilbaecher Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone PNAS, August 28, 2007; 104(35): 14062 - 14067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Hu, S. Dai, W.-J. Wu, W. Tan, X. Zhu, J. Mu, Y. Guo, R. Bolli, and G. Rokosh Stromal Cell Derived Factor-1{alpha} Confers Protection Against Myocardial Ischemia/Reperfusion Injury: Role of the Cardiac Stromal Cell Derived Factor-1{alpha} CXCR4 Axis Circulation, August 7, 2007; 116(6): 654 - 663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Trushin, A. Algeciras-Schimnich, S. R. Vlahakis, G. D. Bren, S. Warren, D. J. Schnepple, and A. D. Badley Glycoprotein 120 Binding to CXCR4 Causes p38-Dependent Primary T Cell Death That Is Facilitated by, but Does Not Require Cell-Associated CD4 J. Immunol., April 15, 2007; 178(8): 4846 - 4853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Fernando, H. Hu, H. Ni, J. A. Hoxie, and D. Weissman Vaccine-delivered HIV envelope inhibits CD4+ T-cell activation, a mechanism for poor HIV vaccine responses Blood, March 15, 2007; 109(6): 2538 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yasuda, T. Kuwabara, H. Nakano, K. Aritomi, T. Onodera, M. Lipp, Y. Takahama, and T. Kakiuchi Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells Blood, January 15, 2007; 109(2): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-h. Lee, T. Kakinuma, J. Wang, H. Zhang, D. C. Palmer, N. P. Restifo, and S. T. Hwang Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy of immunotherapy for established lung metastases. Mol. Cancer Ther., October 1, 2006; 5(10): 2592 - 2599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goda, H. Inoue, H. Umehara, M. Miyaji, Y. Nagano, N. Harakawa, H. Imai, P. Lee, J. B. MaCarthy, T. Ikeo, et al. Matrix Metalloproteinase-1 Produced by Human CXCL12-Stimulated Natural Killer Cells Am. J. Pathol., August 1, 2006; 169(2): 445 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cassan, E. Piaggio, J. P. Zappulla, L. T. Mars, N. Couturier, F. Bucciarelli, S. Desbois, J. Bauer, D. Gonzalez-Dunia, and R. S. Liblau Pertussis Toxin Reduces the Number of Splenic Foxp3+ Regulatory T Cells J. Immunol., August 1, 2006; 177(3): 1552 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ghaffari, D. L. Tuttle, D. Briggs, B. R. Burkhardt, D. Bhatt, W. A. Andiman, J. W. Sleasman, and M. M. Goodenow Complex Determinants in Human Immunodeficiency Virus Type 1 Envelope gp120 Mediate CXCR4-Dependent Infection of Macrophages J. Virol., November 1, 2005; 79(21): 13250 - 13261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-W. Kim, R. L. Ferris, and T. L. Whiteside Chemokine C Receptor 7 Expression and Protection of Circulating CD8+ T Lymphocytes from Apoptosis Clin. Cancer Res., November 1, 2005; 11(21): 7901 - 7910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Cabioglu, J. Summy, C. Miller, N. U. Parikh, A. A. Sahin, S. Tuzlali, K. Pumiglia, G. E. Gallick, and J. E. Price CXCL-12/Stromal Cell-Derived Factor-1{alpha} Transactivates HER2-neu in Breast Cancer Cells by a Novel Pathway Involving Src Kinase Activation Cancer Res., August 1, 2005; 65(15): 6493 - 6497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kucia, R. Reca, K. Miekus, J. Wanzeck, W. Wojakowski, A. Janowska-Wieczorek, J. Ratajczak, and M. Z. Ratajczak Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF-1-CXCR4 Axis Stem Cells, August 1, 2005; 23(7): 879 - 894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Basu and H. E. Broxmeyer Transforming growth factor-{beta}1 modulates responses of CD34+ cord blood cells to stromal cell-derived factor-1/CXCL12 Blood, July 15, 2005; 106(2): 485 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fukuda, H. E. Broxmeyer, and L. M. Pelus Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1{alpha}(CXCL12)/CXCR4 axis Blood, April 15, 2005; 105(8): 3117 - 3126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Badr, G. Borhis, D. Treton, and Y. Richard IFN{alpha} enhances human B-cell chemotaxis by modulating ligand-induced chemokine receptor signaling and internalization Int. Immunol., April 1, 2005; 17(4): 459 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. B. Irby, R. L. Malek, G. Bloom, J. Tsai, N. Letwin, B. C. Frank, K. Verratti, T. J. Yeatman, and N. H. Lee Iterative Microarray and RNA Interference-Based Interrogation of the Src-Induced Invasive Phenotype Cancer Res., March 1, 2005; 65(5): 1814 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Jaleel, A. C. Tsai, S. Sarkar, P. V. Freedman, and L. P. Rubin Stromal cell-derived factor-1 (SDF-1) signalling regulates human placental trophoblast cell survival Mol. Hum. Reprod., December 1, 2004; 10(12): 901 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Liang, T. Wu, H. Lou, X. Yu, R. S. Taichman, S. K. Lau, S. Nie, J. Umbreit, and H. Shim Inhibition of Breast Cancer Metastasis by Selective Synthetic Polypeptide against CXCR4 Cancer Res., June 15, 2004; 64(12): 4302 - 4308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kawada, M. Sonoshita, H. Sakashita, A. Takabayashi, Y. Yamaoka, T. Manabe, K. Inaba, N. Minato, M. Oshima, and M. M. Taketo Pivotal Role of CXCR3 in Melanoma Cell Metastasis to Lymph Nodes Cancer Res., June 1, 2004; 64(11): 4010 - 4017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Holm, C. Zhang, P. R. Gorry, K. Peden, D. Schols, E. De Clercq, and D. Gabuzda Apoptosis of Bystander T Cells Induced by Human Immunodeficiency Virus Type 1 with Increased Envelope/Receptor Affinity and Coreceptor Binding Site Exposure J. Virol., May 1, 2004; 78(9): 4541 - 4551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vitale, A. Schmid-Alliana, V. Breuil, M. Pomeranz, M.-A. Millet, B. Rossi, and H. Schmid-Antomarchi Soluble Fractalkine Prevents Monocyte Chemoattractant Protein-1-Induced Monocyte Migration via Inhibition of Stress-Activated Protein Kinase 2/p38 and Matrix Metalloproteinase Activities J. Immunol., January 1, 2004; 172(1): 585 - 592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Kayali, K. Van Gunst, I. L. Campbell, A. Stotland, M. Kritzik, G. Liu, M. Flodstrom-Tullberg, Y.-Q. Zhang, and N. Sarvetnick The stromal cell-derived factor-1{alpha}/CXCR4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas J. Cell Biol., November 24, 2003; 163(4): 859 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Murakami, A. R. Cardones, S. E. Finkelstein, N. P. Restifo, B. A. Klaunberg, F. O. Nestle, S. S. Castillo, P. A. Dennis, and S. T. Hwang Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10 J. Exp. Med., November 3, 2003; 198(9): 1337 - 1347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Rao, M. P. Quinones, E. Garavito, Y. Kalkonde, F. Jimenez, C. Gibbons, J. Perez, P. Melby, W. Kuziel, R. L. Reddick, et al. CC Chemokine Receptor 2 Expression in Donor Cells Serves an Essential Role in Graft-versus-Host-Disease J. Immunol., November 1, 2003; 171(9): 4875 - 4885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Smit, P. Verdijk, E. M. H. van der Raaij-Helmer, M. Navis, P. J. Hensbergen, R. Leurs, and C. P. Tensen CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase Blood, September 15, 2003; 102(6): 1959 - 1965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Chalasani, F. Baribaud, C. M. Coughlan, M. J. Sunshine, V. M. Y. Lee, R. W. Doms, D. R. Littman, and J. A. Raper The Chemokine Stromal Cell-Derived Factor-1 Promotes the Survival of Embryonic Retinal Ganglion Cells J. Neurosci., June 1, 2003; 23(11): 4601 - 4612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lu, Y. Nakamoto, Y. Nemoto-Sasaki, C. Fujii, H. Wang, M. Hashii, Y. Ohmoto, S. Kaneko, K. Kobayashi, and N. Mukaida Potential Interaction between CCR1 and Its Ligand, CCL3, Induced by Endogenously Produced Interleukin-1 in Human Hepatomas Am. J. Pathol., April 1, 2003; 162(4): 1249 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Bruna-Romero, J. Schmieg, M. Del Val, M. Buschle, and M. Tsuji The Dendritic Cell-Specific Chemokine, Dendritic Cell-Derived CC Chemokine 1, Enhances Protective Cell-Mediated Immunity to Murine Malaria J. Immunol., March 15, 2003; 170(6): 3195 - 3203. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
