Function Scaffold protein
1 function
1.1 tethering signaling components
1.2 localization of signaling components in cell
1.3 coordinating positive , negative feedback
1.4 insulating correct signaling proteins inactivation
function
scaffold proteins act in @ least 4 ways: tethering signaling components, localizing these components specific areas of cell, regulating signal transduction coordinating positive , negative feedback signals, , insulating correct signaling proteins competing proteins.
tethering signaling components
this particular function considered scaffold s basic function. scaffolds assemble signaling components of cascade complexes. assembly may able enhance signaling specificity preventing unnecessary interactions between signaling proteins, , enhance signaling efficiency increasing proximity , effective concentration of components in scaffold complex. common example of how scaffolds enhance specificity scaffold binds protein kinase , substrate, thereby ensuring specific kinase phosphorylation. additionally, signaling proteins require multiple interactions activation , scaffold tethering may able convert these interactions 1 interaction results in multiple modifications. scaffolds may catalytic interaction signaling proteins may result in allosteric changes of these signaling components. such changes may able enhance or inhibit activation of these signaling proteins. example ste5 scaffold in mitogen-activated protein kinase (mapk) pathway. ste5 has been proposed direct mating signaling through fus3 mapk catalytically unlocking particular kinase activation mapkk ste7.
localization of signaling components in cell
scaffolds localize signaling reaction specific area in cell, process important local production of signaling intermediates. particular example of process scaffold, a-kinase anchor proteins (akaps), target cyclic amp-dependent protein kinase (pka) various sites in cell. localization able locally regulate pka , results in local phosphorylation pka of substrates.
coordinating positive , negative feedback
many hypotheses how scaffolds coordinate positive , negative feedback come engineered scaffolds , mathematical modeling. in three-kinase signaling cascades, scaffolds bind 3 kinases, enhancing kinase specificity , restricting signal amplification limiting kinase phosphorylation 1 downstream target. these abilities may related stability of interaction between scaffold , kinases, basal phosphatase activity in cell, scaffold location, , expression levels of signaling components.
insulating correct signaling proteins inactivation
signaling pathways inactivated enzymes reverse activation state and/or induce degradation of signaling components. scaffolds have been proposed protect activated signaling molecules inactivation and/or degradation. mathematical modeling has shown kinases in cascade without scaffolds have higher probability of being dephosphorylated phosphatases before able phosphorylate downstream targets. furthermore, scaffolds have been shown insulate kinases substrate- , atp-competitive inhibitors.
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