High impact information on Guk1

• Structural characterization of the intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95 [1].
• In hippocampal neurons, altered accumulation of PIP3 by overexpression of GAKIN constructs led to the loss of the axonally differentiated neurites [2].
• Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity [2].
• Recombinant GAKIN and PIP3BP form a complex on synthetic liposomes containing PIP3 and support the motility of the liposomes along microtubules in vitro [2].
• The membrane-associated guanylate kinase PSD-95 scaffolds N-methyl-d-aspartate receptors to cytoplasmic signaling molecules, and associates with other glutamate receptors at central synapses [3].

Biological context of Guk1

• Here, the GK domain was subcloned, expressed as an intein fusion protein, purified without the intein and then crystallized at room temperature by the hanging-drop vapour-diffusion method using PEG 8000 as a precipitant [4].
• The structures show that the beta-subunit core contains two interacting domains: a Src homology 3 (SH3) domain and a guanylate kinase (GK) domain [5].

Anatomical context of Guk1

• The membrane-associated guanylate kinase proteins have been known to interact various membrane receptors with their N-terminal segments designated the PDZ domains and to cluster these receptors at the target site of the cell membrane [6].
• Zonula occludens 2 (ZO-2) protein is a tight-junction phos phorylated protein that belongs to the membrane-associated guanylate kinase ('MAGUK') family [7].
• Localization of BAI-associated protein1/membrane-associated guanylate kinase-1 at adherens junctions in normal rat kidney cells: polarized targeting mediated by the carboxyl-terminal PDZ domains [8].
• The GFP-BAP1 mutant containing either the first PDZ and GK domains or the WW and second PDZ domains was localized in the cytosol and the nucleus [8].
• Recent studies have shown that the membrane-associated guanylate kinase protein, zonula occludens-1 (ZO-1) can bind to catenins in epithelial cells and act as an adapter for the transport of the connexin isotype, Cx43 during gap junction formation [9].

Associations of Guk1 with chemical compounds

• Inhibition of rat hepatic guanylate kinase by 6-thioguanosine-5'-phosphate and 6-selenoguanosine-5'-phosphate [10].
• Guanylate kinase does not interfere with the purification of hypoxanthine phosphoribosyltransferase on GMP agarose and moreover is itself partially purified by this chromatography [11].
• The syndecan family of cell surface heparan sulfate proteoglycans interacts via their cytoplasmic C-terminal tail with the PDZ domain of CASK/LIN-2, a membrane-associated guanylate kinase homolog [12].

Other interactions of Guk1

• No effect was detected for other members of the membrane-associated guanylate kinase protein family, such as SAP102 and PSD-95 [13].
• p55 is a membrane-associated guanylate kinase (MAGuK) family member that consists of a single PDZ followed by SH3, HOOK and guanylate kinase (GuK or GK) domains [14].
• Structure of the SH3-guanylate kinase module from PSD-95 suggests a mechanism for regulated assembly of MAGUK scaffolding proteins [15].
• Junctional adhesion molecule (JAM) 4 is a member of immunoglobulin superfamily that interacts with MAGI-1, a membrane-associated guanylate kinase protein at tight junctions in epithelial cells [16].
• Here, we test this hypothesis by assessing whether the GK domain in SAP97 encodes an authentic guanylate kinase [17].

Analytical, diagnostic and therapeutic context of Guk1

• Crystallization and preliminary X-ray diffraction studies of the guanylate kinase-like domain of PSD-95 protein from rat [4].

References