PRAM-1 is required for optimal integrin-dependent neutrophil function

Regina A. Clemens, Sally A. Newbrough, Elaine Y. Chung, Shereen Gheith, Andrew L. Singer, Gary A. Koretzky, Erik J. Peterson

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Abstract

PML-retinoic acid receptor alpha (RARα) 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 Fcγ 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.

Original languageEnglish (US)
Pages (from-to)10923-10932
Number of pages10
JournalMolecular and cellular biology
Volume24
Issue number24
DOIs
StatePublished - Dec 1 2004

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

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. https://doi.org/10.1128/MCB.24.24.10923-10932.2004