Identification of a thyroid hormone receptor that is pituitary-specific

Three cellular homologs of the v-erbA oncogene were previously identified in the rat; two of them encode high affinity receptors for the thyroid hormone triiodothyronine (T3). A rat complementary DNA clone encoding a T3 receptor form of the ErbA protein, called r-ErbA beta-2, was isolated. The r-ErbA beta-2 protein differs at its amino terminus from the previously described rat protein encoded by c-erbA beta and referred to as r-ErbA beta-1. Unlike the other members of the c-erbA proto-oncogene family, which have a wide tissue distribution, r-erbA beta-2 appears to be expressed only in the anterior pituitary gland. In addition, thyroid hormone downregulates r-erbA beta-2 messenger RNA but not r-erbA beta-1 messenger RNA in a pituitary tumor-derived cell line. The presence of a pituitary-specific form of the thyroid hormone receptor that may be selectively regulated by thyroid hormone could be important for the differential regulation of gene expression by T3 in the pituitary gland.     

Sequence and expression of human estrogen receptor complementary DNA

The mechanism by which the estrogen receptor and other steroid hormone receptors regulate gene expression in eukaryotic cells is not well understood. In this study, a complementary DNA clone containing the entire translated portion of the messenger RNA for the estrogen receptor from MCF-7 human breast cancer cells was sequenced and then expressed in Chinese hamster ovary (CHO-K1) cells to give a functional protein. An open reading frame of 1785 nucleotides in the complementary DNA corresponded to a polypeptide of 595 amino acids and a molecular weight of 66,200, which is in good agreement with published molecular weight values of 65,000 to 70,000 for the estrogen receptor. Homogenates of transformed Chinese hamster ovary cells containing a protein that bound [3H]estradiol and sedimented as a 4S complex in salt-containing sucrose gradients and as an 8 to 9S complex in the absence of salt. Interaction of this receptor-[3H]estradiol complex with a monoclonal antibody that is specific for primate ER confirms the identity of the expressed complementary DNA as human estrogen receptor. Amino acid sequence comparisons revealed significant regional homology among the human estrogen receptor, the human glucocorticoid receptor, and the putative v-erbA oncogene product. This suggests that steroid receptor genes and the avian erythroblastosis viral oncogene are derived from a common primordial gene. The homologous region, which is rich in cysteine, lysine, and arginine, may represent the DNA-binding domain of these proteins.     

Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system

A complementary DNA clone derived from rat brain messenger RNA has been isolated on the basis of homology to the human thyroid hormone receptor gene. Expression of this complementary DNA produces a high-affinity binding protein for thyroid hormones. Sequence analysis and the mapping of this gene to a distinct human genetic locus indicate the existence of multiple human thyroid hormone receptors. Messenger RNA from this gene is expressed in a tissue-specific fashion with highest levels in the central nervous system.     

The LDL receptor gene: a mosaic of exons shared with different proteins

The multifunctional nature of coated pit receptors predicts that these proteins will contain multiple domains. To establish the genetic basis for these domains (LDL) receptor. This gene is more than 45 kilobases in length and contains 18 exons, most of which correlate with functional domains previously defined at the protein level. Thirteen of the 18 exons encode protein sequences that are homologous to sequences in other proteins: five of these exons encode a sequence similar to one in the C9 component of complement; three exons encode a sequence similar to a repeat sequence in the precursor for epidermal growth factor (EGF) and in three proteins of the blood clotting system (factor IX, factor X, and protein C); and five other exons encode nonrepeated sequences that are shared only with the EGF precursor. The LDL receptor appears to be a mosaic protein built up of exons shared with different proteins, and it therefore belongs to several supergene families.     

Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily

Apolipoprotein AI (apoAI) is a lipid-binding protein that participates in the transport of cholesterol and other lipids in the plasma. A complementary DNA clone for a protein that bound to regulatory elements of the apoAI gene was isolated. This protein, designated apoAI regulatory protein-1 (ARP-1), is a novel member of the steroid hormone receptor superfamily. ARP-1 bound to DNA as a dimer, and its dimerization domain was localized to the COOH-terminal region. ARP-1 also bound to a thyroid hormone-responsive element and to regulatory regions of the apoB, apoCIII, insulin, and ovalbumin genes. In cotransfection experiments, ARP-1 downregulated the apoAI gene. The involvement of ARP-1 in the regulation of apoAI gene expression suggests that it may participate in lipid metabolism and cholesterol homeostasis.     

禽类生长激素受体基因研究进展

生长激素受体(GHR)是促乳素、生长激素、细胞因子、促红细胞生成素受体超家族成员之一,它与生长激素(GH)结合可对禽类生长发育起到调节作用.目前有关禽类GHR的研究多集中在正常鸡和矮小禽类之间GHR的变异上.本文就鸡GHR基因结构与表达、多态性与生产性能的相关等研究进行了综述和讨论.     

All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner

In mammals different isoforms of myosin heavy chain are encoded by the members of a multigene family. The expression of each gene of this family is regulated in a tissue- and developmental stage-specific manner as well as by hormonal and various pathological stimuli. In this study the molecular basis of isoform switches induced in myosin heavy chain by thyroid hormone was investigated. The expression of the myosin heavy chain gene family was analyzed in seven different muscles of adult rats subjected to hypo- or hyperthyroidism with complementary DNA probes specific for six different myosin heavy chain genes. The results demonstrate that all six genes are responsive to thyroid hormone. More interestingly, the same myosin heavy chain gene can be regulated by thyroid hormone in highly different modes, even in opposite directions, depending on the tissue in which it is expressed. Furthermore, the skeletal embryonic and neonatal myosin heavy chain genes, so far considered specific to these two developmental stages, can be reinduced by hypothyroidism in specific adult muscles.     

Two G protein oncogenes in human endocrine tumors

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.     

beta-Arrestin: a protein that regulates beta-adrenergic receptor function

Homologous or agonist-specific desensitization of beta-adrenergic receptors is thought to be mediated by a specific kinase, the beta-adrenergic receptor kinase (beta ARK). However, recent data suggest that a cofactor is required for this kinase to inhibit receptor function. The complementary DNA for such a cofactor was cloned and found to encode a 418-amino acid protein homologous to the retinal protein arrestin. The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors.     

Nucleotide sequence of a human Blym transforming gene activated in a Burkitt's lymphoma

The nucleotide sequence of a human Blym-1 transforming gene activated in a Burkitt's lymphoma cell line was determined. This sequence predicts a small protein of 58 amino acids that is 33 percent identical to the predicted product of chicken Blym-1, the activated transforming gene of chicken B cell lymphomas. Both the human and chicken Blym-1 genes exhibit significant identity to an amino-terminal region of transferrins.     

1,25-dihydroxyvitamin D-responsive element and glucocorticoid repression in the osteocalcin gene

The active hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3[1,25(OH), which regulates cellular replication and function in many tissues and has a role in bone and calcium homeostasis, acts through a hormone receptor homologous with other steroid and thyroid hormone receptors. A 1,25(OH)2D3-responsive element (VDRE), which is within the promoter for osteocalcin [a bone protein induced by 1,25(OH)2D3] is unresponsive to other steroid hormones, can function in a heterologous promoter, and contains a doubly palindromic DNA sequence (TTGGTGACTCACCGGGTGAAC; -513 to -493 bp), with nucleotide sequence homology to other hormone responsive elements. The potent glucocorticoid repression of 1,25(OH)2D3 induction and of basal activity of this promoter acts through a region between -196 and +34 bp, distinct from the VDRE.