Enzyme-Linked Receptors

4 Key excerpts on "Enzyme-Linked Receptors"

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  eBook - PDF

  Exploring the Cell Membrane: Conceptual Developments

  • A. Kleinzeller(Author)
  • 2012(Publication Date)
  • Elsevier Science

    (Publisher)

  The regulation of receptor function at the biochemical level, ranging from re-ceptor synthesis and turnover to receptor modulation by phos-phorylation-dephosphorylation reactions is every bit as com-plex as the regulation of conventional enzyme pathways (e.g. see Hollenberg, 1985; 1987). The knowledge of receptor func-tion at the biochemical and cellular level that has been achieved over the past 30 years now provides an excellent foundation for future work aimed at understanding the overall integrated function of multicellular organisms. Surely, this picture of receptor function that has been developed would have delighted Clark, Ehrlich, Langley and their colleagues. In a sense, the information that is presently being published about receptor structure and function now represents an em-barassment of riches. The rate of appearance of new informa-tion has begun to exceed the rate of assimilating the data, even for a single superfamily of receptors, such as the G-pro-tein-linked 'serpentine' receptor class. Thus, in the near fu-ture, it is hoped that within a receptor superfamily, it will be possible to identify discrete domains in common that may be associated with functions that are in common between related receptors. For instance, certain sequences within the G-pro-tein-coupled receptor family are highly conserved (see Sav-arese and Fraser, 1992). It is expected that the precise func-tion of many of these conserved residues and sequences will soon been clarified. Alternately, it is anticipated that the unique receptor domains that result in the ligand specificity of MEMBRANE RECEPTORS 217 a given receptor will be readily identified by a variety of molec-ular approaches, as outlined elsewhere (Hollenberg, 1991). As rapidly as information is appearing about receptor struc-ture, so is information about receptor-triggered signal transduction pathways expanding almost exponentially.

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  The Membranes of Cells

  • Philip L. Yeagle(Author)
  • 2016(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 15

  Membrane Receptors

  Abstract

  The membranes of cells, in particular the plasma membrane of cells, contain membrane proteins that are dedicated to provide communication between the outside and the inside of the cell. This is the process called signal transduction. Among many such receptors, several are introduced in this chapter including receptors that function by receptor-mediated endocytosis, receptor tyrosine kinases, ligand-gated ion channels, adhesion receptors, and G-protein coupled receptors. Low-density lipoprotein enters cells through receptor-mediated endocytosis, as does transferrin. The insulin receptor is a tyrosine kinase. The kinase activity is activated by insulin binding to the receptor. The nicotinic acetylcholine receptor is a ligand-gated ion channel that opens in response to binding acetylcholine. Integrins are members of the family of adhesion receptors, that both signal and mediate attachment to the extracellular matrix. A large family of receptors mediates signals through G proteins, the G-protein coupled receptors. Both rhodopsin and the β-adrenergic receptor mediate signaling through G proteins.

  Keywords

  LDL receptor; transferrin receptor; insulin receptor; nicotinic acetylcholine receptor; integrin; guanylyl cyclase receptors; G-protein coupled receptor; rhodopsin

  The plasma membranes of cells separate the inside of the cells from the outside of the cells. The communication that must occur between the environment surrounding the cell and the interior of the cell must be mediated by the plasma membrane. The communication may be in response to extracellular signals from the immediate environment or from the organism as a whole.

  The process whereby signals external to the cell alter intracellular behavior is called signal transduction. The signals can be hormones or other molecular species that reach the cell surface, often from other parts of the same organism. In one specialized kind of communication, the signal is a photon of light.

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  Molecular Endocrinology

  • Franklyn F. Bolander(Author)
  • 2004(Publication Date)
  • Academic Press

    (Publisher)

  Fig. 4-1 ).

  Fig. 4-1 The four major groups of integral membrane receptors: (A) Enzyme-Linked Receptors, (B) cytokine receptors, (C) G protein-coupled receptors, and (D) ligand-gated ion channels.

  Like the nuclear receptors, the Enzyme-Linked Receptors are also relatively simple in structure: they have an amino-terminal extracellular domain, a single transmembrane α-helix, and a carboxy-terminal intracellular domain that contains an intrinsic enzymatic activity, such as a tyrosine kinase, a serine-threonine kinase, or a guanylate cyclase. In the case of the receptor tyrosine kinase (RTK), the hormone binds to the amino terminus and induces aggregation. This brings the catalytic domains, which have low basal activity, close enough to cross-phosphorylate each other’s activation loop, resulting in full kinase activity. The serine-threonine kinase receptors are activated in a similar manner. However, activation of the membrane-bound guanylate cyclases, which synthesize 3′5′-cyclic GMP (cGMP), is less clear but appears to involve ligand-induced neutralization of an autoinhibitory domain in the cytoplasmic region.

  The major substrate for the RTK is itself; the phosphorylated tyrosines (pYs) attract effectors, which have special binding modules that recognize pYs. For this brief introduction, only three are mentioned: phospholipase C? (PLCγ), phophatidylinositol-3 kinase (PI3K), and docking proteins.

  PLCγ hydrolyzes membrane phosphoinositides to yield the soluble head group inositol 1,4,5-trisphosphate (IP3 ) and diacylglycerol (DG) (Fig. 4-2 ). The former opens calcium channels, which elevate cytoplasmic calcium concentrations. Although calcium can affect proteins directly, it more frequently acts through calmodulin (CaM), a calcium-binding protein. The CaM-dependent protein kinase, type II (CamKII), is a classic example of how CaM works. The CaMKII has an autoinhibitory domain that acts as a pseudosubstrate for both the adenosine 5’ -triphosphate (ATP) and the catalytic sites. The CaM binding site is adjacent to the autoinhibitory domain. When calcium levels rise, calcium binds CaM and exposes its protein-binding site; CaM then binds to CaMKII and prevents the autoinhibitory domain from occupying the ATP and catalytic sites, thereby activating the kinase. Many enzymes, channels, and other proteins have these CaM binding-autoinhibitory domains. The DG is also a second messenger; its best-known target is protein kinase C (PKC), also called calcium-activated, phospholipid-dependent protein kinase

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  Medical Biochemistry

  • Gustavo Blanco, Antonio Blanco(Authors)
  • 2017(Publication Date)
  • Academic Press

    (Publisher)

  Chapter 25 Biochemical Basis of Endocrinology (I) Receptors and Signal Transduction Abstract Cells express receptors, which can be located inside the cell or at the plasma membrane. Intracellular receptors can be in the nucleus and cytosol. They bind nonpolar or weakly polar molecules (steroid hormones, thyroid hormones, active metabolites of vitamin D, and retinoids), which can easily cross the cell plasma membrane. Once the hormone-receptor complex (HR) forms, it dimerizes and binds to specific DNA sequences (hormone responsive elements), modifying their transcription. Peroxisome proliferator activated receptor (PPAR) is a nuclear receptor that functions as a transcription factor. It regulates metabolic pathways and the cell cycle. Membrane receptors are localized on the cell surface. Upon ligand binding, these receptors undergo conformational changes that are transmitted to protein intermediates of a signal cascade system. They belong to different types: (1) G protein coupled receptors have seven transmembrane segments. G proteins are αβγ heterotrimers, which under basal conditions are inactive, bound to GDP. After binding of the ligand to the receptor, it interacts with a G protein causing the replacement of GDP for GTP, which frees the α-GTP subunit and allows it to activate downstream effectors. The βγ dimer can also act as an intermediate in the signaling process. (2) Tyrosine kinase coupled receptors (TK) consist of an extracellular segment with the ligand-binding site, one transmembrane helix, and a cytoplasmic portion containing kinase activity. Formation of the ligand receptor complex promotes dimerization of the receptor, activates its autophosphorylation and promotes the binding of cell signaling proteins. (3) Receptors associated with extrinsic TK are similar to the ones mentioned previously, but lack the catalytic site. They associate to tyrosine kinase when bound to the ligand

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