Multiple signaling pathways have been documented for the TPR. A variety of signaling pathways activated by the TPR have been determined using the nonerythropoietic tissue-protective compounds CEPO and pHBSP. Tissue-protective receptor occupancy leads to JAK-2 phosphorylation which subsequently activates a number of divergent cascades. In some tissues, these pathways overlap and are therefore redundant; but in others, each appears to serve specific functions. Both enhanced (blue boxes) and suppressed (red boxes) responses have been identified (see text for discussion).