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

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.

SLP-76 regulates Fcgamma receptor and integrin signaling in neutrophils.

While the contribution of intracellular adaptor proteins to lymphocyte activation has been well studied, the function of these molecules in innate immune effector cells such as neutrophils has not been extensively addressed. Here we demonstrate a critical role for the adaptor molecule SH2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76) in FcgammaR and integrin signaling. Stimulation of these receptors induces tyrosine phosphorylation and cytoplasmic relocalization of SLP-76 in freshly isolated murine neutrophils.