Evidence for a role for SAM68 in the responses of human neutrophils to ligation of CD32 and to monosodium urate crystals

SAM68 (Src-associated in mitosis 68 kDa) is a member of the signal transduc tion of activator RNA novel gene family coding for proteins postulated to b e involved in signal transduction and activation of RNA. It has been implic ated through its phosphorylation status in the control of the transition fr om the G(1) to the S phases during mitosis. However, the implication and ro le of SAM68 in nonproliferative cells are unknown. The present study was in itiated to examine the role of SAM68 in the phagocytic responses of the ter minally differentiated human neutrophils. The results obtained show that SA M68 is present in human neutrophils and that it is tyrosine phosphorylated in response to stimulation by monosodium orate crystals or by ligation of C D32. Stimulation of neutrophils by these agonists decreases the association of SAM68 with Sepharose-conjugated poly-U beads. Additionally, the amount of immunoprecipitable SAM68 was modulated differentially after stimulation by monosodium urate crystals or by CD32 engagement indicating that the post translational modifications and/or protein associations of SAM68 induced by these two agonists differed. The results of this study provide evidence fo r an involvement of SAM68 in signal transduction by phagocytic agonists in human neutrophils and indicate that SAM68 may play a role in linking the ea rly events of signal transduction to the posttranscriptional modulation of RNA.