Canonical pathways

Cellular phosphoinositide concentrations are under tight control by phospholipid kinases and phosphatases. Phospholipid kinases preferentially phosphorylate distinct positions of the inositol ring and hence are subdivided into phosphoinositide 3-kinases (PI3Ks), phosphoinositide 4-kinases (Pl4Ks), and phosphoinositide 5-kinases (PI5Ks) that phosphorylate Pis on position 3, 4 and 5, respectively. In a canonical pathway, Ptdlns... 

Computational methods have been applied to determine the connections in systems that are not well-defined by canonical pathways. This is either done by semi-automated and/or curated literature causal modeling [1] or by statistical methods based on large-scale data from expression or proteomic studies (a mostly theoretical approach is given by reference [2] and a more applied approach is in reference [3]). Many methods, including clustering, Bayesian analysis and principal component analysis have been used to find relationships and "fingerprints" in gene expression data [4]. 

FIGURE 7 Top-scored metabolite-centric network generated by Ingenuity Pathway Analysis (IPA) describing amino acid metabolism, molecular transport, and small-molecule biochemistry. Microarray results were overlaid in the network highlighting associations between metabolites and transcripts in different canonical pathways (CP). Underlined molecules were downregulated not underlined molecules were upregulated Alp, p70 S6k, and AMPK (marked with an asterisk) were not altered. Reproduced from Ref. (20). 

Within the CNS, the transcriptionally active form of NF-kB is mostly the p50/RelA heterodimer (Bhakar et al., 2002 Schmidt-Ullrich et al., 1996). NF-kB exists in a latent and a constitutively active form in neurons. The constitutive NF-kB is within the nucleus, it is transcriptionally active and regulated by synaptic activity (Kaltschmidt et al., 1994 Meffert et al., 2003 Schmidt-Ullrich, et al., 1996). The latent form is sequestered in the cytoplasm through its interaction with an inhibitory protein l/r.B. Two different intracellular pathways activate NF-kB, the classic and the alternative pathway, which result in the release of NF-k.B from its inhibitors, IkB, and in the nuclear localization of NF-kB (Bonizzi and Karin, 2004). The canonical pathway of NF-kB activation involves an IkB kinase (IKK) complex, composed of two catalytic subunits, IKK 1 /a and IKK2/ft, and a regulatory subunit NF-kB essential modulator (NEMOyiKKq. Upon... 

Pathway analysis of gene expression data need not be restricted to only canonical pathways. Generally, the interactions described in the literature among gene products, proteins, and small molecules can be extracted from the literature and visualized as networks. Natural language processing (NLP)... 

Pathways Analysis (table 7.1) contains a large set of manually curated gene and protein interactions, together with multiple viewers to display various aspects of the interactions. Both canonical pathways (i.e., generally accepted functional units) and arbitrary interaction networks can be displayed, and links to annotation data and to literature citations are accessible from the viewers. 

The alternative TCR-dependent signalling cascade used by SAgs converges with the canonical Lck-dependent pathway at the level of ERK-1/2 activation, as indicated by the observation that blockade of activation of ERK-1/2 inhibits T cell responses to these toxins (fig. 2). Downstream, one finds activation and translocation of NF-AT and NF-kB, both in Lck-deficient and in Lck-expressing T cells. Of interest, the contribution of the canonical pathway to this alternative pathway at the level of the activation of ERK-1/2 seems to be primarily quantitative because the magnitude of ERK-1/2 activation in the absence of Lck is lower but the temporal profile of activation is comparable [41],... 

The Wnt/wingless family of signaling molecules are involved in diverse ontogenic processes. In the canonical pathway, the Wnt signal is transduced... 

P-arrestins are originally identified as negative regulators of G protein-coupled receptors (GPCR). P-arrestin-1 and -2 are required for cellular communication by means of Wnts and FZDs. In canonical pathway, P-arrestins participate in the formation of a ternary complex composed of phosphorylated Dvl, P-arrestin and Axin, and affect the transcriptional activity of TCF/LEF (Schulte et al, 2010). It is not clear whether P-arrestin serves only as a scaffolding protein or whether P-arrestin-dependent endocytosis is required. 

The function of Wnt signaling pathway in synapses has been characterized during neuronal development. Wnts play roles in the formation of the sensory-motor connections in mouse spinal cord. Wnt-3 and 7a can promote synaptogenesis inducing the clustering of synapsin 1, a presynaptic protein involved in synapse formation and fimction. This effect is controlled by the canonical pathway and can be mimicked by the GSK-3P inhibition induced by... 

---