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Article
PRAM-1 is Required for Optimal Integrin-Dependent Neutrophil Function.
Molecular and cellular biology
  • Regina A Clemens
  • Sally A Newbrough
  • Elaine Y Chung
  • Shereen Gheith, Lehigh Valley Health Network
  • Andrew L Singer
  • Gary A Koretzky
  • Erik J Peterson
Publication/Presentation Date
12-1-2004
Abstract
PML-retinoic acid receptor alpha (RARalpha) 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 Fcgamma 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.
Disciplines
PubMedID
15572693
Document Type
Article
Citation Information

Clemens, R. A., Newbrough, S. A., Chung, E. Y., Gheith, S., Singer, A. L., Koretzky, G. A., & Peterson, E. J. (2004). PRAM-1 is required for optimal integrin-dependent neutrophil function. Molecular And Cellular Biology, 24(24), 10923-10932.