Partial characterization of a cerebral thyroid hormone-responsive protein.
The thyroid hormone-responsive protein (THRP) is expressed in rat cerebral tissue and has 83% overall sequence homology with c-Abl interactor protein, Abi-2, which is a substrate for the tyrosine kinase activity of c-Abl. Within the core region of the two proteins, the sequence similarity approaches 99%. To determine whether THRP is a rat homologue of Abi-2 or is a distinct protein with unique properties, the tissue distribution of THRP and Abi-2 mRNA's was examined using a sensitive ribonuclease protection assay and probes specific for THRP and Abi-2, respectively. The THRP mRNA content of cerebral tissue (1340.0 +/- 126.5 arbitrary units) was 2.3-fold higher than Abi-2 mRNA (581.3 +/- 73.7), while the ratio of hepatic content of THRP mRNA (209.0 +/- 49.1) to hepatic Abi-2 mRNA (2923.0 +/- 378.7) was only 0.07 (P < 0.004). Very low levels of Abi-2 mRNA, but not THRP mRNA, were also found in the heart and small intestine. Experiments with PC12 cells transfected with the full-length THRP cDNA and grown in the presence or absence of a tyrosine kinase inhibitor, along with experiments where PC12 cells were cotransfected with the THRP cDNA with or without the wild-type or mutant (tyrosine kinase deficient) c-Abl cDNA, showed that THRP is tyrosine phosphorylated; however, it is not a substrate for c-Abl. These studies demonstrate that THRP and Abi-2 have distinct tissue distribution and distinct biological properties.
Haas
Michael J
MJ
Division of Endocrinology, Diabetes and Metabolism, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Li
Jian-Ping
JP
Pun
Kristoffer
K
Mooradian
Arshag D
AD
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000737:chemistry*; D018398:Homeodomain Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014162:Transfection
C490756:Abi2 protein, mouse; C109099:Abi2 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D016315:Proto-Oncogene Proteins c-abl