Abstract
Somatic mutation of signal transduction genes or key nodes of the cellular protein network can cause severe diseases in humans but can sometimes genetically improve plants, likely because growth is determinate in animals but indeterminate in plants. This article reviews protein networks; human protein ranking; the mitogen-activated protein kinase (MAPK) and insulin (phospho- inositide 3kinase [PI3K]/phosphatase and tensin homolog [PTEN]/protein kinase B [AKT]) signaling pathways; human diseases caused by somatic mutations to the PI3K/PTEN/ AKT pathway; use of the MAPK pathway in plant molecular breeding; and protein domain evolution. Casitas B-lineage lymphoma (CBL), PTEN, MAPK1 and PIK3CA are among PIK3CA the top-ranked proteins in directional rankings. Eight proteins (ACVR1, CDC42, RAC1, RAF1, RHOA, TGFBR1, TRAF2, and TRAF6) are ranked in the top 50 key players in both signal emission and signal reception and in interaction with many other proteins. Top-ranked proteins likely have major impacts on the network function. Such proteins are targets for drug discovery, because their mutations are implicated in various cancers and overgrowth syndromes. Appropriately managing food intake may help reduce the growth of tumors or malformation of tissues. The role of the protein kinase C/ fatty acid synthase pathway in fat deposition in PTEN/PI3K patients should be investigated. Both the MAPK and insulin signaling pathways exist in plants, and MAPK pathway engineering can improve plant tolerance to biotic and abiotic stresses such as salinity.
Highlights
MAPKKKK mitogen-activated protein kinase kinase kinase kinase miRNA microRNA messenger RNAs (mRNAs) messenger RNA mTOR mechanistic target of rapamycin
It is challenging to trace how novel protein domains were generated from existing ones, Li et al (2011) were able to conclude that all the intermediate domains during the generation of type II proteinase inhibitor (PIII)-7C/6C domains in the potato (Solanum tuberosum) proteinase inhibitor family were likely functional because the intermediate protein domains responded to selection during the emergence of that group of closely related PIII-7C/6C novel domains
We tentatively suggest that the protein kinase C (PKC)/sterol regulatory element-binding protein (SREBP)/fatty acid synthase (FAS) pathway is involved in the accumulation of lipomatous tissue in a mass
Summary
In non-directional ranking, nodes tend to be ranked higher whenever the total number of their incoming and outgoing links combined is higher (Du et al, 2012) When this algorithm is applied to a protein network, the top-ranked proteins in forward ranking are key "workers" or key information receivers, because those proteins are the large nodes receiving signals or information flows from other proteins or receiving actions from proteins that are large nodes in the network. High-ranking proteins in the human protein network The proteins ranked in the top 50 by the forward, reverse, and non-directional rankings are mainly MAPK signaling pathway proteins (account for 35%, 30%, and 24%, repectively) and insulin signaling pathway proteins (account for 18%, 16%, and 20%, respectively) (Table 1) (Du et al, 2012). The position of the R side chain was not calculated via energy minimization, but merely reflects the most common rotamer for R
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