Intracellular Signal Transduction Mechanisms

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

Numerous studies have shown that EGF binding to EGFR triggers receptor dimerization. This is considered a crucial step in intracellular signal transduction [98]. Inspired by this mechanism, we designed EGF chimeric proteins that spontaneously dimerized (dEGF-His). These dimers were terminally anchored to the substrate. We expected that these preformed dimeric EGF structures would facilitate the formation of EGF-EGFR dimer complexes more efficiently than monomeric EGF structures. 

The signal transduction mechanisms by which most interleukins prompt their biological response are understood, in outline at least. In many cases, interleukin cell surface receptor binding is associated with intracellular tyrosine phosphorylation events. In other cases, serine and threonine residues of specific intracellular substrates are also phosphorylated. For some interleukins,... 

The exact molecular mechanisms by which TNF-induced signal transduction are mediated remain to be characterized in detail. Oligomerization of the receptors is often followed by their phosphorylation, most likely by accessory kinases that associate with the intracellular domain of the receptor (neither receptor type displays intrinsic protein kinase activity). The existence of several phosphoproteins capable of associating with (the intracellular domain of) TNF-R55 and TNF-R75 have also been established. Following clustering of the TNF receptors, these... 

The EPO receptor is a member of the haemopoietic cytokine receptor superfamily. Its intracellular domain displays no known catalytic activity, but it appears to couple directly to the JAK2 kinase (Chapter 8) that likely promotes the early events of EPO signal transduction. Other studies have implicated additional possible signalling mechanisms, including the involvement of G proteins, protein kinase C and Ca2+. The exact molecular events underlining EPO signal transduction remain to be elucidated in detail. 

Molecular mechanisms underlying the early- and late-phase expressions of LTP. While opening the NMDA receptors is crucial for coincidence-detection, the sensitivity and robustness of coincidence-detection is not solely determined by the opening time-window. It is dependent on at least three other features summation of the opening duration, the peak amplitude and proper intracellular signal transduction. 

Animal cells are separated from each other by lipid membranes. During signal transduction this barrier has to be passed, which can be realized by permanently or temporarily opened channels or by an indirect mechanism without material flux between the extra- and intracellular lumen (Fig. 1). 

Sulfation in most aspects is very similar to phosphorylation, except that sulfation is not involved in intracellular signal transduction, but in other forms of signaling. The mechanism of sulfation is similar to that of phosphorylation as a general base from the enzyme active site that deprotonates the hydroxyl groups of tyrosine residues. The nucleophilic oxygen then attacks the /3-position, in contrast to the 7-position in phosphorylation, and releases adenosine 3, 5 -diphosphate. 

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