PRAM-1 is required for optimal integrin-dependent neutrophil function. Academic Article uri icon

Overview

MeSH

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Calcium
  • Cell Degranulation
  • Gene Expression
  • Gene Targeting
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Opsonin Proteins
  • Phagocytosis
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Respiratory Burst
  • Sequence Homology, Amino Acid
  • Staphylococcus aureus

MeSH Major

  • Integrins
  • Neutrophils
  • Proteins

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.

publication date

  • December 2004

has subject area

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Calcium
  • Cell Degranulation
  • Gene Expression
  • Gene Targeting
  • Humans
  • Integrins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Neutrophils
  • Opsonin Proteins
  • Phagocytosis
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Proteins
  • Respiratory Burst
  • Sequence Homology, Amino Acid
  • Staphylococcus aureus

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC533979

Digital Object Identifier (DOI)

  • 10.1128/MCB.24.24.10923-10932.2004

PubMed ID

  • 15572693

Additional Document Info

start page

  • 10923

end page

  • 10932

volume

  • 24

number

  • 24