Signal-transduction molecules

Some intracellular signal transduction molecules are reduced in schizophrenia 883... 

Some intracellular signal transduction molecules are reduced in schizophrenia. The release of neurotransmitters is regulated by a family of proteins that coordinate vesicular trafficking (see Ch. 9). Of these, the expression of complexin I and II appears to be decreased in prefrontal cortex and subfields of the hippocampal formation, and the ratio of complexin I to complexin II is elevated in the hippocampus [35], SNAP-25 (Synaptosomal Associated Protein, kDa 25) has inconsistently been found to be down-regulated in both these regions. Synapsin expression is also reduced, but more robust decrements have been observed in bipolar disorder (Ch. 55). 

Lioubin, M.N., Algate, P.A., Tsai, S., Carlberg, K., Aebersold, R., and Rohrschneider, L.R., 1996, pl50 P, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity. Genes Dev. 10 1084-1095. 

Intracellular Signal Transduction Molecules as Potential Therapeutic Targets... 

There are multiple phospholipase C s (PLCs) that are linked via G-proteins to neurotransmitter receptors. PLCs split the link between the Sn3 carbon and the phosphorus, thus generating two molecules the headgroup phosphate and diacylglycerol (DAG). PLCs particularly act on inositol phospholipids, generating inositol phosphates and DAG. As in the PLA2 cycle, both of these products are active signal transduction molecules. Again, the cycle must be terminated as shown in Fig. 2, by means of inositol phosphatases and DAG kinases. 

During neuronal stimulation, the activation of multiple phospholipases seems to be the norm and it can be very difficult to sort out the interactions among them. For example, whereas PA generated by PLD is a potent signal transduction molecule, it can be further metabolized to Lyso-PA, another signal transduction molecule with different effects, by the actions of PLA2. Lyso-PA can be converted back to PA by lysophosphafidic acid acyl transferase (LPAAT), and PA can be converted to DAG by phosphatidate phosphohydro-lase. These are just a few examples of the complex interactions that can occur during neuronal activation. 

Figure 9-3 Structures of compounds that affect Rho-family GTPases and downstream signal transductions. Molecules in parentheses are targets of small molecules.

CD5 is a signal transduction molecule present on the surface of most thymocytes and immature peripheral T cells. It is also detectable on a small subset of circulating B cells, and its primary use in diagnostic immu-nohistochemistry is in the detection of malignancies derived from those cells B-cell CLL/SLL and mantle cell lymphoma (Fig. 6.6A and B). Antigen retrieval is necessary. 

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