Monday, October 12, 2009
cytoplasmic receptors-unit-7-cell signalling-cellbiology-btechbiotechnology
Cytoplasmic receptor: proteins in the cytoplasm or nucleus that specifically bind signaling molecules and trigger changes which influence the behavior of cells; major groups are the steroid hormone receptors, which usually are found in the cytoplasm, and the thyroid hormone receptors, which usually are found in the nucleus; not all cytoplasmic receptors are tree'd under this term.
types of receptors include:
* antigen receptor
* complement receptor
* cytokine receptor
Antigen receptor: family of immunoglobin-like lymphocyte surface molecules that mediate activation of lymphocytes by antigens.
Complement receptor: molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
Cytokine receptor: cell surface proteins that bind cytokines and trigger intracellular changes; postcoordinate with specific cytokine where appropriate.
Glucocorticoids induce tyrosine aminotransferase (EC 18.104.22.168) synthesis in cultured rat hepatoma cells. These steroids penetrate the cell membrane and bind to specific cytoplasmic receptor proteins. The resulting complex binds to the nucleus, produces a confirmational; change and results in the geneactivation process .This shows that steroid hormones stimulate the synthesis of specific proteins by affecting the transcription of structural or regulatory genes.
Proteins in the cytoplasm or nucleus that specifically bind signaling molecules and trigger changes which influence the behavior of cells. The major groups are the steroid hormone receptors.
Steroid hormone receptors are found on the plasma membrane, in the cytosol and also in the nucleus of target cells. They are generally intracellular receptors (typically cytoplasmic) and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. Some steroid hormone receptors are part of the nuclear receptor family that include a group of homologous structured receptors (type II receptors) that bind to non-steroid ligands such as thyroid hormones and vitamin A, as well as to vitamin D, and orphan receptors. All these receptors are transcription factors.
* Type I Receptors
o Sex hormone receptors (sex hormones)
+ Androgen receptor
+ Estrogen receptor
+ Progesterone receptor
o Glucocorticoid receptor (glucocorticoids)
o Mineralocorticoid receptor (mineralocorticoids)
* Type II Receptors
o Vitamin A receptor (Vitamin A)
o Vitamin D receptor (Vitamin D)
o Retinoid receptor:Retinoid receptors are nuclear receptors (a class of proteins) that bind to retinoids. When bound to a retinoid, they act as transcription factors, altering the expression of genes with corresponding response elements.
* Orphan receptors:An orphan receptor is an apparent receptor that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan".
Intracellular steroid hormone receptors share a common structure of four units that are functionally homologous, so-called "domains":
1. Variable domain: It begins at the N-terminal and is the most variable domain between the different receptors.
2. DNA binding domain: This centrally located highly conserved DNA binding domain (DBD) consists of two non-repetitive globular motifs (PDB: 1HCQ) where zinc is coordinated with four cysteine and no histidine residues. Their secondary and tertiary structure is distinct from that of classic zinc fingers. This region controls which gene will be activated. On DNA it interacts with the hormone response element (HRE).
3. Hinge region: This area controls the movement of the receptor to the nucleus.
4. Hormone binding domain: The moderately conserved ligand-binding domain (LBD) can include a nuclear localization signal, amino-acid sequences capable of binding chaperones and parts of dimerization interfaces. Such receptors are closely related to chaperones (namely heat shock proteins hsp90 and hsp56), which are required to maintain their inactive (but receptive) cytoplasmic conformation. At the end of this domain is the C-terminal. The terminal connects the molecule to its pair in the homodimer or heterodimer. It may affect the magnitude of the response.
Free (that is, unbound) steroids enter the cell cytoplasm and interact with their receptor. In this process heat shock protein is dissociated, and the activated receptor-ligand complex is translocated into the nucleus.
After binding to the ligand (steroid hormone), steroid receptors often form dimers. In the nucleus the complex acts as transcription factors, augmenting or suppressing transcription of particular genes by its action on DNA. As a result messenger RNA is produced that exits the nucleus and interacts with ribosomes. There, after translation of the genetic message, specific proteins are produced. These specific proteins perform a biological task.