High impact information on Pira1

• Activating PIR-A and inhibitory PIR-B are expressed in a wide range of cells in the murine immune system, such as B cells, mast cells, macrophages, and dendritic cells, mostly in a pair-wise fashion [1].
• Thus, PIR-A and PIR-B are indispensable for the regulation of cellular signaling and important for homeostasis of the immune system [1].
• PIR-A-induced dendritic cell activation also led to increased proliferation of donor cytotoxic T cells [2].
• PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively, by multiple Pira genes and a single Pirb gene in mice, are relatives of the human natural killer (NK) and Fc receptors [3].
• Whereas PIR-B fibroblast transfectants expressed cell surface molecules of approximately 120 kD, PIR-A transfectants expressed the approximately 85-kD molecules exclusively intracellularly; PIR-A and FcRgammac cotransfectants expressed the PIR-A/ FcRgammac complex on their cell surface [3].

Biological context of Pira1

• To explore the phylogenetic history of the murine paired Ig-like receptors of activating (PIR-A) and inhibitory (PIR-B) types, we isolated PIR homologues from a rat splenocyte cDNA library [4].
• Southern blot analysis predicts the presence of multiple Pira genes and a single Pirb gene in the rat genome [4].
• These results provide important clues to the coordinate regulation observed for PIR-A and PIR-B expression during hematopoiesis [5].
• The Pir genes appear to be distributed in three regions of the proximal end of chromosome 7 based on the present data and an analysis of currently available mouse genomic sequence databases [5].

Anatomical context of Pira1

• The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloid lineage cells, wherein both are expressed simultaneously [6].
• Cross-linking of this PIR-A complex results in mast cell activation such as calcium mobilization in an ITAM-dependent manner [7].
• A diverse pattern of polymorphism is defined for the paired Ig-like receptors (PIRs) that serve as activating (PIR-A) and inhibitory (PIR-B) receptors on B lymphocytes, dendritic cells, and myeloid-lineage cells in mice [8].
• Although PIR-B's inhibitory pathway has been described, it is unknown whether PIR-A receptors can deliver activation signals to macrophages, and if so, through what mechanism [9].
• Murine PIR-A and -B can be immunoprecipitated from the RAW264.7 macrophage cell line, and murine PIR-A can be immunoprecipitated from the J774.A1 line using B27(2) [10].

Associations of Pira1 with chemical compounds

• Although mast cells produced both PIR-A and PIR-B, PIR-B was found to be preferentially expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with intracellular SHP-1 protein tyrosine phosphatase [11].
• A charged arginine in the transmembrane region of PIR-A suggests its potential association with other transmembrane proteins to form a signal transducing unit [12].

Other interactions of Pira1

• One region contains a single Pir gene which is almost identical to Pira6, and the other two contain multiple Pir genes in opposite transcriptional orientations [5].
• The PIR-A requires the homodimeric Fc receptor common gamma chain for its efficient cell-surface expression and for the delivery of an activation signal [13].
• Mast cells produce PIR-A and PIR-B, but PIR-B was found to be predominantly expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with SHP-1 tyrosine phosphatase [14].
• Here we show that Fc receptor gamma chain, containing an immunoreceptor tyrosine-based activation motif (ITAM), associates with PIR-A [7].

Analytical, diagnostic and therapeutic context of Pira1

• Thus, PIR-A and PIR-B are counteracting receptors that are essential for successful tissue transplantation and may regulate irrelevant reaction to autologous tissues in a constitutive way in physiological conditions [2].
• Southern blot analysis with PIR-B and PIR-A-specific probes suggests only one PIR-B gene and multiple PIR-A genes [6].
• Paired Ig-like receptors, named PIR-A and PIR-B, are predicted from sequence analysis of the cDNAs isolated from a mouse splenic library [6].

References