| First Author | Clemens RA | Year | 2004 |
| Journal | Mol Cell Biol | Volume | 24 |
| Issue | 24 | Pages | 10923-32 |
| PubMed ID | 15572693 | Mgi Jnum | J:95253 |
| Mgi Id | MGI:3525750 | Doi | 10.1128/MCB.24.24.10923-10932.2004 |
| Citation | Clemens RA, et al. (2004) PRAM-1 is required for optimal integrin-dependent neutrophil function. Mol Cell Biol 24(24):10923-32 |
| abstractText | 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. |
