The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13.
Extracts from human Jurkat cells or from calf thymus contain a 60-kDa protein that is bound to immobilized FK506. As expected, the NH2-terminal sequences of the 60-kDa protein from these two species were found to be nearly the same. We were surprised to discover, however, that the sequence of the human protein was identical to that of Hsp56, a heat shock protein of unknown function that has been shown to be a component of several steroid receptor complexes. Further analysis of the calf thymus protein revealed a peptide with homology to a region near the COOH terminus of both FKBP-12 and FKBP-13. It would appear, therefore, that this 60-kDa protein, or as we refer to it provisionally, "Hsp56," could have the capacity to bind FK506 directly. These observations lead us to speculate that "Hsp56" may mediate immunosuppression and inhibition of T-cell proliferation by FK506 and may do so via a cytosolic signal transduction pathway separate, but not necessarily exclusive, from that of FKBP-12 and FKBP-13.
Department of Biochemistry, Upjohn Company, Kalamazoo, Michigan 49001.
A W
AW
Yem
A G
AG
Tomasselli
R L
RL
Heinrikson
H
H
Zurcher-Neely
V A
VA
Ruff
R A
RA
Johnson
M R
MR
Deibel
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D016559:Tacrolimus / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins; D013950:Thymus Gland / Q000378:metabolism*
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D011987:Receptors, Steroid; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus