Antigen receptor signalling: from the membrane to the nucleus

this issue, Ref. 1). Ligation of the BCR induces protein tyrosine kinase (PTK) activity I-s, as well zs phospholipase C (PLC)-mediated hydrolysis of phos- phatidylinositol (4,5)-bisphosphate (PIP2)to generate inositol (1,4,5)-trisphosphate (IP 3) and diacylglycerol (DAG) (Refs 1,6). IP 3 mobilizes intracellular stores of calcium ([Ca2+]0, leading to activation of calcium/ calmodulin-dependent protein kinase II (CaM-KII), and DAG is an activator of the ~, 13 and ~ isoforms of protein kinase C (PKC) (~, 13, ~, l~ and "q isoforms are expressed in B cellsV). Although the data are controversial, genetic and biochemical studies I,sq° indicate that the primary signal in this pathway may be the activation of the sIg-associated PTK p72 ~yk, resulting in the binding and activation of a srorelated PTK(s) that, in turn, tyrosine phos- phorylates conserved sequences termed antigen- receptor homology 1 (ARH1) motifs in the cyto- plasmic domains of Ig-a and Ig-13 (Refs 1,11). This induces recruitment of additional p72 ~yk, as well as the reorientation and enhanced binding and acti- vation of the ARHl-associated