UNASSIGNED: @entity6 is strongly associated with @entity73 , but the molecular reasons are unknown. We found that fasting and peripheral insulin promote phosphorylation and dephosphorylation, respectively, of specific residues on brain proteins that included cytoskeletal regulators such as slit-robo GTPase-activating protein 3 ( @entity68956 ) and microtubule affinity-regulating protein kinases (MARKs), whose @entity10204 are linked to @entity16 . Fasting activates protein kinase A (PKA) but not PKB/Akt signaling in the brain, and PKA can phosphorylate the purified @entity68956 . The phosphorylation of @entity68956 and MARKs were increased when PKA signaling was activated in primary neurons. Knockdown of PKA decreased phosphorylation of @entity68956 . Furthermore, @entity68957 , an @entity37799 ( @entity37799 ), can form a complex with @entity68956 and PKA in the brain of fasted @entity19 to facilitate the phosphorylation of @entity68956 by PKA. Although brain cells have insulin receptors, our findings are inconsistent with the down-regulation of phosphorylation of target proteins being mediated by insulin signaling within the brain. Rather, our findings infer that systemic insulin through a yet unknown mechanism inhibits PKA or protein kinase(s) with similar specificity and/or activates an unknown phosphatase in the brain. Ser(858) of @entity68956 was identified as a key regulatory residue, whose phosphorylation by PKA enhanced the GAP activity of @entity68956 towards its substrate @entity5844 in cells, thereby inhibiting the action of this GTPase in cytoskeletal regulation. Our findings reveal novel mechanisms linking peripheral insulin sensitivity with cytoskeletal remodelling in neurons, which may help to explain the association of @entity6 with @entity16 such as @entity195 ( @entity195 ).

Fasting and systemic insulin signaling regulate phosphorylation of brain proteins that modulate cell morphology and link to XXXX .

@entity6 :: ('MESH:D003920', 'Disease') :: ['Diabetes', 'diabetes'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive decline'] @entity16 :: ('MESH:D009422', 'Disease') :: ['neurological disorders'] @entity37799 :: ('11640(Tax:10090)', 'Gene') :: ['AKAP', 'A-kinase anchoring protein'] @entity10204 :: ('MESH:D021081', 'Disease') :: ['deficiency or dysregulation'] @entity5844 :: ('19353(Tax:10090)', 'Gene') :: ['Rac1'] @entity68957 :: ('83767(Tax:10090)', 'Gene') :: ['WAVE1'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity68956 :: ('259302(Tax:10090)', 'Gene') :: ['srGAP3']
@entity16 :: (MESH:D009422,Disease) :: ['neurological disorders']
