Identification of mitogen-activated protein kinase docking sites in enzymes that metabolize phosphatidylinositols and inositol phosphates

Abstract

Background: Reversible interactions between the components of cellular signaling pathways allow for the formation and dissociation of multimolecular complexes with spatial and temporal resolution and, thus, are an important means of integrating multiple signals into a coordinated cellular response. Several mechanisms that underlie these interactions have been identified, including the recognition of specific docking sites, termed a D-domain and FXFP motif, on proteins that bind mitogen-activated protein kinases (MAPKs). We recently found that phosphatidylinositol-specific phospholipase C-γ1 (PLC-γ1) directly binds to extracellular signal-regulated kinase 2 (ERK2), a MAPK, via a D-domain-dependent mechanism. In addition, we identified D-domain sequences in several other PLC isozymes. In the present studies we sought to determine whether MAPK docking sequences could be recognized in other enzymes that metabolize phosphatidylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs).

Genome-Wide Epistatic Interaction Networks Affecting Feed Efficiency in Duroc and Landrace Pigs

“…The systemic effects mediated by thyroid hormones induces metabolic shifts characterized by increased lipolysis and gluconeogenesis, affecting feed efficiency in pigs (Reyer et al, 2017a). MAPKs regulates (either stimulating or inhibiting) the catalytic activity, and specificity, of kinases and phosphatases that are involved in the metabolism of phosphatidylinositols (PI) and inositol phosphates (IP), thereby exert regulatory actions on PIand/or IP-dependent signaling pathways (Caldwell et al, 2006). Genes P14KB and PLCB1 which accelerated to Inositol phosphate metabolism were associated with phosphate metabolism and feed efficiency in Duroc (Ding et al, 2018).…”

SAC1 lipid phosphatase and growth control of the secretory pathway

“…6,9 However, the function of the various intracellular organelles and the rate of trafficking between them must be coupled to cell growth and cell division and there is increasing evidence that these compartment-specific phosphoinositide pools can be modulated in response to extracellular signals. 33,34 Site-specific biosynthesis and turnover by lipid kinases and phosphatases are essential for dynamic regulation of the various phosphoinsositide pools. 35 Yet, how the individual trafficking routes that are governed by phosphoinositides are synchronized in coordination with growth and proliferation is poorly understood.…”

Recognition of sites of functional specialisation in all known eukaryotic protein kinase families

“…Clearly, knowledge of such sites finds immense application in designing kinase-specific inhibitors, protein engineering and recognition of interaction partners. Such sites should ideally be identified by traditional experimental methods like mutation studies and structural analyses using X-ray diffraction; but these are evidently slow processes as in-depth information on family-specific functional sites is so far known only for a few kinase families such as PKA [ 18 ], Src [ 19 ], MAPK [ 20 ] and CDK [ 21 , 22 ]. In this scenario, we have analysed the sequences of all known STY kinases, comprehensively studied the conservation patterns within and across kinase families, devised a unified scheme and identified kinase family-specific functional sites in each of them.…”