The research described here focuses on human cDNAs and genes that encode FKBP (FK506 binding protein) and FKBP-related proteins. FKBP is an abundant cytosolic protein that binds with high affinity to the immunosuppressants FK506 and rapamycin, compounds that inhibit T lymphocyte signal transduction pathways. FKBP is an attractive candidate for the functional in vivo receptor of these drugs, an obvious key modulator of T cell activation.
The aims of this work draw strongly upon techniques of nucleic acid hybridization, DNA sequencing and PCR analysis and are to (i) search for additional classes of human FKBP transcripts, (ii) sequence all FKBP exons within the human gene(s) and determine the splicing patterns that produce the FKBP transcript family and (iii) search for human cDNAs that encode functional and structural analogs of FKBP. These goals address molecular and biochemical aspects of FKBP function and could define diagnostic tools to monitor patient response to FK506 or FK506-like immunosuppressants and could provide marketable probes for identifying additional proteins involved in regulating T cell activation. The research also could identify transcripts that encode cellular receptors responsible for FK506/rapamycin-like immunomodulatory actions or receptors that modulate other actions in a similar biochemical manner, thereby defining additional targets for novel therapeutics.
