This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Clemens, R. A. Articles by Peterson, E. J. Search for Related Content PubMed PubMed Citation Articles by Clemens, R. A. Articles by Peterson, E. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2004, p. 10923-10932, Vol. 24, No. 24
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.24.10923-10932.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

PRAM-1 Is Required for Optimal Integrin-Dependent Neutrophil Function

Regina A. Clemens,^1,2, Sally A. Newbrough,^1,2, Elaine Y. Chung,¹ Shereen Gheith,^1,3 Andrew L. Singer,¹ Gary A. Koretzky,^1,3* and Erik J. Peterson^1,

Abramson Family Cancer Research Institute,¹ Medical Scientist Training Program,² Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania³

Received 30 June 2004/ Returned for modification 19 August 2004/ Accepted 23 September 2004

PML-retinoic acid receptor alpha (RAR) regulated adaptor molecule 1 (PRAM-1) is an intracellular adaptor molecule that is upregulated during the induced granulocytic differentiation of promyelocytic leukemic cells and during normal human myelopoiesis. This report describes the generation of PRAM-1-deficient mice and an analysis of the function of this adaptor in neutrophil differentiation and mature neutrophil function. We demonstrate here that neutrophil differentiation is not impaired in PRAM-1-deficient mice and that PRAM-1-deficient neutrophils function normally following engagement of Fc receptors. In contrast, mature PRAM-1-null neutrophils exhibit significant defects in adhesion-dependent reactive oxygen intermediate production and degranulation. Surprisingly, other integrin-dependent responses, such as cell spreading and activation of several signaling pathways, are normal. Together, these findings demonstrate the uncoupling of key integrin-dependent responses in the absence of PRAM-1 and show this adaptor to be critical for select integrin functions in neutrophils.

---

* Corresponding author. Mailing address: Dept. of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160. Phone: (215) 746-5522. Fax: (215) 746-5525. E-mail: koretzky{at}mail.med.upenn.edu.

R.A.C. and S.A.N. contributed equally to this work.

Present address: Division of Rheumatology and Department of Medicine, Center for Immunology, University of Minnesota, Minneapolis, MN 55455.

---

Molecular and Cellular Biology, December 2004, p. 10923-10932, Vol. 24, No. 24
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.24.10923-10932.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Ward, P. P., Mendoza-Meneses, M., Park, P. W., Conneely, O. M. (2008). Stimulus-Dependent Impairment of the Neutrophil Oxidative Burst Response in Lactoferrin-Deficient Mice. Am. J. Pathol. 172: 1019-1029 [Abstract] [Full Text]  
• Bach, T. L., Chen, Q.-M., Kerr, W. T., Wang, Y., Lian, L., Choi, J. K., Wu, D., Kazanietz, M. G., Koretzky, G. A., Zigmond, S., Abrams, C. S. (2007). Phospholipase Cbeta Is Critical for T Cell Chemotaxis. J. Immunol. 179: 2223-2227 [Abstract] [Full Text]  
• Utomo, A., Cullere, X., Glogauer, M., Swat, W., Mayadas, T. N. (2006). Vav Proteins in Neutrophils Are Required for Fc{gamma}R-Mediated Signaling to Rac GTPases and Nicotinamide Adenine Dinucleotide Phosphate Oxidase Component p40(phox). J. Immunol. 177: 6388-6397 [Abstract] [Full Text]