Plasma membrane-associated signaling pathways

Besides the genomic pathway, the nongenomic pathway of AR also has been reported in oocytes (57), skeletal muscle cells (58), osteoblasts (59,60), and prostate cancer cells (61,62). As compared to the genomic pathway, the nongenomic actions of steroid receptors are characterized by the rapidity of the action, which varies from seconds to an hour or so, and by interaction with plasma membrane-associated signaling pathways (63). Nevertheless, the structural basis for nongenomic action is direct interactions between AR and cytosolic proteins from different signaling pathways, which could be closely... 

Several examples of proteins involved in signal transduction pathways are reported to be encoded by auxin-induced mRNAs. These include the 3-subunit of a heterotrimeric G-protein (arcA) [105,106], cyclin-dependent protein kinases (cdc2s) [107-111], and calmodulin (PCM-1 and arCAM) [112,113]. Putative transcription factors are also represented in the list of auxin-induced mRNAs. Auxin-responsive cDNA clones for a G-box binding bZIP transcription factor (SGBF-1) [114] and a homeobox transcription factor (Athb-8) have been reported [115]. Another auxin-responsive mRNA, dbp, was proposed to be a lysine-rich nuclear protein similar to HI histone, and the recombinant protein was shown to bind nonspecilically to DNA [116]. The amino acid sequence of dbp is, however, highly similar (i.e., 67% identity and 80% similarity) to a potato plasma membrane-associated protein called remorin [117]. The remorin protein binds to both simple and complex galacturonides as well as DNA, but is not a nuclear protein in potato... 

Hess F, Estrugo D, Fischer A et al (2007) Integrin-linked kinase interacts with caspase-9 and -8 in an adhesion-dependent manner for promoting radiation-induced apoptosis in human leukemia cells. Oncogene 26 1372-1384 Hirao M, Sato N, KondoT etal (1996) Regulation mechanism of ERM (ezrin/radixin/moesin) protein/plasma membrane association possible involvement of phosphatidylinositol turnover and Rho-dependent signaling pathway. J Cell Biol 135 37 51... 

TRAM was the fourth adapter discovered and has only been seen to have a role in TLR-4 signalling. It contains a TIR domain and a myristoylation site. When TRAM is myristoylated it becomes bound to the plasma membrane and can bind to TLR-4 through its TER. domain. TRAM then allows TRIF to bind it and activate the pathways associated with TRIF as outlined above for TLR-3. 

The functions of the calcium-storage capacity of the ER are at least threefold the association of Ca2+ with Ca2+-binding proteins in the ER is part of a chaperone function that is essential for normal protein synthesis the rapid rate of Ca2+ uptake by endoplasmic pumps provides shortterm cytoplasmic Ca2+ buffering that resists untoward and transient changes in [Ca2+] and, finally, many signaling pathways employ elevated [Ca2+] to activate physiological processes. Extensive Ca2+ release from ER is coupled to activation of Ca2+ entry across the plasma membrane, a process known as capacitative calcium entry, which is discussed below. 

A primary function of the SH3 domains is to form fimctional oligomeric complexes at defined subcellular sites, frequently in cooperation with other modular domains. SH3 domains are foimd in many proteins associated with the cytoskeleton or with the plasma membrane. Examples are the actin binding protein a-spectrin and myosin lb. Furthermore, SH3 interactions are involved in signal transduction in the Ras pathway (see Chapter 9). 

Extrinsic (death receptor) pathway of caspase activation during apoptosis involves the binding of death ligands to cell surface receptors (e.g., Fas/ CD95/Apo-l or TNF receptor), recruitment of adaptor molecules Fas-associated death domain (FADD) or TNF receptor-associated death domain (TRADD) to the cytosolic end of the receptor, and formation of the death-inducing signaling complex (DISC) at the plasma membrane. DISC recruits and activates the initiator caspases, caspase-8 or -10. 

When attention is directed toward the phospholipase.C found in mammalian tissue, a rather unique and different substrate profile is evident. It appears that the most favored substrate status must be assigned to the inositol- containing phosphoglycerides, namely, phosphatidylinositol (PI), phosphatidylinositol phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2). There is some evidence that the plasma membrane of certain mammalian cells contains a phospholipase C with high specificity for the bisphosphate, PIP2. The latter enzymatic interaction would be closely associated with the signal transduction pathway in mammalian cells. 

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