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

Research output: Contribution to journalArticle

23 Scopus citations

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 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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