NR AUOD
AU Mazzoni,I.E.; Ledebur,H.C.Jr.; Paramithiotis,E.; Cashman,N.R.
TI Lymphoid signal transduction mechanisms linked to cellular prion protein
QU Biochemistry and Cell Biology 2005 Oct; 83(5): 644-53
PT journal article
AB The normal cellular isoform of the prion protein (PrPc) is a glycosylphosphatidylinositol-anchored cell surface protein that is expressed widely, including in lymphoid cells. We compared lectin-induced mitogenesis and selected cell signaling pathways in splenocytes from wild-type BALB/c mice and Zrch Prnp0/0 (PrP0/0) mice bred on a BALB/c background for more than 10 generations. 3H-thymidine incorporation induced by concanavalin A (Con A) or phytohemagglutinin (PHA) was significantly reduced in PrP0/0 splenocytes, most prominently early in activation (24 and 48 h). Con A activation in PrP0/0 splenocytes was associated with differences in the phosphorylation (P) patterns of protein kinase C (PKC alpha/beta, but not delta) and the PKC downstream effectors p44/42MAPK (mitogen-activated protein kinase). P-PKC and P-MAPK profiles were similar in wild-type and PrP0/0 splenocytes following PMA treatment, indicating that the ability of these 2 enzymes to be phosphorylated is not impaired in the absence of PrPc. Con A-induced calcium fluxes, monitored by indo-1 fluorescence, were equivalent in PrP0/0 and PrP+/+ splenocytes, suggesting that calcium-dependent mechanisms are not directly implicated in the differential phosphorylation patterns or mitotic responses. Our data indicate that PrP0/0 splenocytes display defects in upstream or downstream mechanism(s) that modulate PKCalpha/beta phosphorylation, which in turn affects its capacity to regulate splenocyte mitosis, consistent with a role for PrPc in immune function.
MH Animals; Blotting, Western; Calcium/metabolism; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases/metabolism; PrPc Proteins/*metabolism; Protein Kinase C/metabolism; Spleen/cytology
AD Caprion Pharmaceuticals, Montreal, QC H4S 2C8, Canada.
SP englisch
PO Kanada