Cell surface, receptor/ligand binding

Kinetics of Cell Surface Receptor-Ligand Binding ... 

The most critical step in these experiments is the choice of the site for fluorescent labeling. All labels, in particular however the large GFP variants, carry the risk of impairing the function and disposition of the labeled protein, and care must be taken to assure that indeed the labeled protein retains essential properties of the parent protein, such as cell surface expression, ligand binding, and signaling in the case of receptors. The choice of the insertion site is facilitated by structural information, and by knowledge about functional sites in these structures. 

Receptors are very dynamic in their active presence at the cell surface. Both ligand binding and alterations in gene function can alter the number, half-life, and responsiveness of... 

Fig. 9. Receptor binding in three geometric situations, (a) Binding of ligand to receptors free in solution, (b) Binding of ligand to cell surface receptors, (c) Binding of cell surface molecules (X) to cell surface receptors. The radius of an encounter complex is s, the cell radius is a, a typical distance between molecule X and a receptor R is b, and r is the radial position.

Adrenergic receptors Cell-surface receptors that bind epinephrine and norepinephrine. There are several different types with somewhat different ligand specificities and effects (The term comes from adrenaline, the old name for epinephrine.)... 

G Protein Families. Cell responses to the binding of stimulatory ligands (L) to cell-surface receptors (R) proceed through a multistep... 

Real-time spectroscopic methods can be used to measure the binding, dissociation, and internalization of fluorescent ligands with cell-surface receptors on cells and membranes. The time resolution available in these methods is sufficient to permit a detailed analysis of complex processes involved in cell activation, particularly receptor-G protein dynamics. A description of the kinetics and thermodynamics of these processes will contribute to our understanding of the basis of stimulus potency and efficacy. 

Uptake of protein by hepatocytes can occur via one of two mechanisms (a) receptor-mediated en-docytosis or (b) non-selective pinocytosis, again with subsequent protein proteolysis. Similarly, a proportion of some proteins are likely degraded within the target tissue, as binding to their functional cell surface receptors triggers endocytotic internalization of the receptor ligand complex (Figure 4.7). 

Table 8.6 Ligands which, upon binding to their cell surface receptors, are known to promote activation of one or more STATs. (The STATs activated are also shown.) This list, though representative, is not exhaustive...

The neurotrophins interact with two distinct cell surface receptor species [5,6,9] (Fig. 27-2). The neurotrophins bind to the Trk family of receptors, which serve as the principal signal transducer for this class of growth factors. The Trk receptors comprise a small, highly related family of molecules that possess an extracellular ligand binding domain that selectively interacts with the individual neurotrophin species. Trk A specifically binds NGF, TrkB interacts with BDNF and NT4/5, and TrkC preferentially binds NT3. Importantly, the Trk receptors have an intracellular tyrosine kinase domain that is activated upon neurotrophin binding. The kinase domains of the Trk family members are highly conserved and the Trks differ mainly in the structure of their extracellular domains. Trk receptor expression is limited to neurons and the... 

FIGURE 27-3 Neurotrophic cytokines and their receptors. Neurotrophic cytokines are related to IL6 and bind to cell surface receptor complexes that share a common structural organization. The four ligands interchangeably employ two distinct receptor subunits, leukemia inhibitory factor receptor 3 (LIF-Rpt) andgpl30, and some employ a ligand-specific a subunit. CNTF-R, ciliary neurotrophic factor CT-fR.cardiotrophin 1 receptor IL6-R, interleukin-6 receptor. 

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