Other allosteric activators include glutamate and other dicarboxylic acids. Eukaryotic transcriptional activators have separate DNA-binding and activating functions. Ligands include substrates, inhibitors, activators, signaling lipids, and neurotransmitters. ETS factors act as transcriptional repressors, transcriptional activators, or both. These include accelerants, activators, retarders and inhibitors. PRPP and ATP are also allosteric activators of orotate synthesis. Phosphorylated tyrosine residues act as binding sites for intracellular signal activators such as Ras. Cdc2 activity is further regulated by phosphorylation/dephosphorylation of its corresponding activators and inhibitors. PAMPs are known to be potent activators of innate immune signaling. PAI-1, however, is the main inhibitor of the plasminogen activators. Infectious agents are considered T cell activators, a step needed for activation of autoimmune diseases. The main enzyme responsible for this process (plasmin) is regulated by various activators and inhibitors. The transcription activators and the ubiquitin ligases both contain pairs of WW domains. ATIs are potent activators of the innate immune system. Translational activators are encoded in the nucleus.