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MAGUKMembrane-Associated Guanylate Kinase
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Abbreviations: AMPAR, a-amino-3-hydroxy-5-methy1-4-isoxazolepro-pionic acid receptor; LTD, long-term depression; LIP, long-term potentiation; MAGUK, membrane-associated guanylate kinase protein; NMDAR.
Well-described signaling domains in the carboxy terminus include binding and phosphorylation sites for alpha calcium-calmodulin kinase type-2 (aCaMKII), a mediator of activity-dependent longterm potentiation (LTP) and long-term depression (LTD) of synaptic efficacy Merrill et at., 2005); phosphorylation sites for the tyrosine kinases, Src and Fyn, that regulate channel function (Sala and Sheng, 1999); an adaptor protein 2 (AP-2) binding site that regulates receptor internalization (YEKL, Lavezzari et at., 2004; Prybylowski et at., 2005); and a proximal ESDV sequence that permits anchoring at PDZ domains of scaffolding proteins (e.g., membrane-associated guanylate kinase proteins, MAGUKs) in the PSD (Sheng, 2001) (Fig.
The positive outcome of the screen was the identification of 9 X-linked ID/MR genes: AP1S2 (adaptor-related protein complex 1, sigma 2 subunit), CUL4B (cullin 4B), BRWD3 (bromodomain and WD repeat domain containing 3), UPF3B [UPF3 regulator of nonsense transcripts homolog B (yeast)], ZDHHC9 (zinc finger, DHHC-type containing 9), SLC9A6 [solute carrier family 9 (sodium/hydrogen exchanger), member 6], SYP (synaptophysin), ZNF711 (zinc finger protein711), and CASK [calcium/calmodulin-dependent serine protein kinase (MAGUK family)].
[7] Human genes: FMR1, fragile X mental retardation 1; AP1S2, adaptor-related protein complex 1, sigma 2 subunit; CUL4B, cullin 4B; BRWD3, bromodomain and WD repeat domain containing 3; UPF3B, UPF3 regulator of nonsense transcripts homolog B (yeast); ZDHHC9, zinc finger, DHHC-type containing 9; SLC9A6, solute carrier family 9 (sodium/hydrogen exchanger), member 6; SYP, synaptophysin; ZNF711, zinc finger protein 711; CASK, calcium/calmodulin-dependent serine protein kinase (MAGUK family).
TCR dependent activation of NF-[kappa]B is mediated by a scaffold protein CARMA1, which belongs to the family of membrane associated guanylate kinases (MAGUK) [38-40].
The C-terminus of Occludin is capable of interacting directly with actin filaments, PKC-, the tyrosine kinase Yes, and PI-3 kinase, as well as with the MAGUK proteins ZO-1, ZO-2, and ZO-3.
Proteins that interact with the cytoplasmic face of SJs include the MAGUK Discs-large (Dlg), members of the Protein 4.1/ Ezrin-moesin-radixin (ERM) family, and Scribble, a protein with multiple PDZ domains and leucine-rich repeats (Fehon et al., 1994; Bilder and Perrimon, 2000; Bossinger et al., 2001).
Similarly, the Q460R substitution falls at the boundary of an SH3 binding domain (42), which may be important for recruiting the scaffolding protein MAGuK and phosphatidylinositol-4 kinase involved in subunit assembly of proteins involved in exocytosis and membrane trafficking (45, 46).