A Hydrophobic Domain of Ca
-modulating Cyclophilin Ligand Modulates Calcium Influx Signaling in T Lymphocytes (*)
- From the (1)Departments of Experimental Oncology and
- (2)Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105 and
- (3)Department of Pediatrics, University of Tennessee, Memphis, Tennessee 38105
- §James S. McDonnell Foundation Scholar, Program for Molecular Medicine in Cancer Research. To whom reprint requests should be addressed: Dept. of Experimental Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105. Tel.: 901-495-2613; Fax: 901-495-2032; mike.holloway{at}stjude.org.
Abstract
Ca
-modulating cyclophilin ligand (CAML) was originally described as a cyclophilin B-binding protein whose overexpression in
T cells causes a rise in intracellular calcium, thus activating transcription factors responsible for the early immune response.
As reported here, structure-function analysis of the CAML gene in Jurkat T cells indicates that two of CAML's putative membrane-spanning
domains are necessary and sufficient for the modulation of intracellular calcium. We propose that the hydrophobic C-terminal
tail of CAML forms its effector domain, thus implicating the N-terminal hydrophilic domain in a regulatory role. These findings
define a novel protein motif that functions in intracellular calcium signaling.
Footnotes
-
↵* This work was supported in part by Cancer Center CORE Grant CA-21765 from the National Institutes of Health, by Grant BE-234 from the American Cancer Society, and by the American Lebanese Syrian Associated Charities (ALSAC). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- CAML
-
Ca
-modulating cyclophilin ligand
- SEAP
-
secreted alkaline phosphatase
- PMA
-
phorbol 12-myristate 13-acetate
- FACS
-
fluorescence-activated cell sorter.
-
- Received September 28, 1995.
- Revision received February 3, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
