muFKBP38: a novel murine immunophilin homolog differentially expressed in Schwannoma cells and central nervous system neurons in vivo

To better understand the process of multistage carcinogenesis in Schwann cells, we have attempted to isolate novel candidate genes involved in neoplastic progression of mouse malignant Schwannoma cells. The semi-differentiated Schwannoma cell line 56-24 and the less differentiated Schwannoma cell line 64-39 were established from peripheral nerve sheath tumors arising in transgenic mice of the MBP/SV40 large T strain Tg29. By using the chemical cross-linking subtraction technique, we have cloned a novel murine cDNA that detects pronounced expression in 56-24 cells but not in 64-39 cells. The longest open reading frame of the cDNA predicts a peptide showing 95% amino acid sequence homology to the recorded sequence of the human immunophilin homolog huFKBPr38, one of a family of proteins that are thought to interface with a wide range of intracellular signal transduction systems. The predicted open reading frame of the corresponding gene, named muFKBP38, encodes a 38 kDa protein that harbors an FK-binding protein (FKBP) domain that is 36% identical to that of muFKBP52, a three-unit tetratricopeptide repeat and a consensus leucine-zipper repeat. Although muFKBP38 mRNA was detected in both neurons and glial cells, pronounced expression of the immunophilin homolog appeared in various classes of neurons associated with the hippocampal formation, as shown by in situ hybridization analysis of adult mouse brains. Taken together, these data indicate that muFKBP38 is (i) a novel potential marker for semi-differentiated Schwannomas, (ii) may form homomultimers and/or interact with other proteins, and (iii) may have a role in neurons associated with memory function.