Plasma membrane-associated signaling

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... 

The three CAAX-signaled modifications increase the overall hydrophobicity of the carboxyl terminus of Ras and are necessary to promote Ras membrane association. However, these modifications alone are not sufficient to direct full plasma membrane association and signaling activity. At least two additional motifs exist at the carboxyl termini of Ras proteins, which serve to facilitate plasma membrane association and direct Ras proteins to discrete membrane subdomains. These motifs function as secondary signals and are composed either of a stretch of basic amino acids (K-Ras4B) or of cysteine(s) that are pahni-toylated (H-Ras, N-Ras, K-Ras4A) and positioned immediately upstream of the CAAX motif (28, 30) (see Fig. 3). The addition of a palmitate fatty acid is catalyzed by a protein acyltransferase, which forms a reversible thioester bond between the cysteine and the pahnitoyl group (31, 32). 

Fusion protein of AKT with an amino-terminal myristoylation signal sequence. This fatty acid modification promotes persistent plasma membrane association and signaling activity. 

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... 

T. Miyagi, T. Wada, K. Yamaguchi, K. Hata, and K. Shiozaki, Plasma membrane-associated siahdase as a cmcial regulator of transmembrane signalling, J. Biochem., 144 (2008) 279-285. 

Katanaev, V.L. and Wymann, M.P. (1998). GTPyS-induced actin polymerization in vitro ATP- and phosphoinositide-independent signaling via Rho-family proteins and a plasma membrane-associated guanine nucleotide exchange factor. /. Cell Sd. Ill, 1583-1594. 

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... 

Fig. 1. The GP Ib-IX-V complex. The complex consists of seven transmembrane polypeptides denoted GP Iba (mol wt 145,000), GP IbP (mol wt 24,000), GPIX (mol wt 17,000) and GP V (mol wt 82,000), in a stoichiometry of 2 2 2 1. The hatched region represents the plasma membrane. The area above the hatched region represents the extracellular space that below represents the cytoplasm. The complex is a major attachment site between the plasma membrane and the cytoskeleton. Two molecules associated with the cytoplasmic domain are depicted a 14-3-3 dimer, which may mediate intracellular signaling, and actin-binding protein, which connects the complex to the cortical cytoskeleton and fixes its position and influences its function.

In the case of L-type Ca2+ channels, they also carry binding sites for Ca2+ antagonist drugs. The accessory a2-5, p, and y subunits stabilize Ca2+ channel function and support its targeting to the plasma membrane. Notably other proteins can associate with the channel complex allowing the formation of signaling complex important for channel targeting and modulation. 

GPCR function has been shown to be regulated by several different mechanisms. The number of receptors on the plasma membrane may be regulated by transcription, mRNA stability, biosynthetic processing, and protein stability. In addition, the function of receptors in the plasma membrane can be influenced by regulatory phosphorylation and by association with other proteins that determine the subcellular location of receptors relative to other signaling molecules. 

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. 

Muscle contraction is initiated by a signal from a motor nerve. This triggers an action potential, which is propagated along the muscle plasma membrane to the T-tubule system and the sarcotubular reticulum, where a sudden large electrically excited release of Ca " into the cytosol occurs. Accessory proteins closely associated with actin (troponins T, I, and C) together with tropomyosin mediate the Ca -dependent motor command within the sarcomere. Other accessory proteins (titin, nebulin, myomesin, etc.) serve to provide the myofibril with both stability... 

Winship IR, Plaa N, Murphy TH (2007) Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J Neurosci 27 6268-6272 Wu MM, Buchanan J, Luik RM, Lewis RS (2006) Ca store depletion causes STIMl to accumulate in ER regions closely associated with the plasma membrane. J Cell Biol 174 803-813 Wyss-Coray T (2006) Inflammation in Alzheimer disease driving force, bystander or beneficial response Nat Med 12 1005-1015... 

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