Disease relevance of AKAP9

• The AKAP9-BRAF fusion was preferentially found in radiation-induced papillary carcinomas developing after a short latency, whereas BRAF point mutations were absent in this group [1].
• AIM: We aimed to determine the BRAF mutation and AKAP9 expression in papillary thyroid carcinomas (PTCs) [2].
• Antibodies developed against a bovine CLIC, p64, immunoprecipitated AKAP350 from HCA-7 colonic adenocarcinoma cell extracts [3].
• Four new methane-oxidizing bacteria have been isolated from marine samples taken at the Hyperion sewage outfall, near Los Angeles, CA [4].
• Hyperion laser thermokeratoplasty for hyperopia [5].

High impact information on AKAP9

• By immunofluorecent labeling with specific antibodies it was demonstrated that AKAP450 localized to centrosomes [6].
• Immunoprecipitation of RII from RIPA-buffer extracts of HeLa cells demonstrated co-precipitation of AKAP450 [6].
• Sequence comparison demonstrated that the open reading frame contained a previously characterized cDNA encoding Yotiao, as well as the human homologue of AKAP120 [6].
• These data reveal previously undescribed actions of Yotiao that occur subsequent to channel phosphorylation and provide evidence that this adaptor protein also may serve as an effector in regulating this important ion channel [7].
• Eleven of the 64 SNPs mapped to genes encoding pivotal components of the growth hormone/insulin-like growth factor (GH-IGF) pathway, including CAMKK1 E375G (OR=1.37, P=5.4x10(-5)), AKAP9 M463I (OR=1.32, P=1.0x10(-4)) and GHR P495T (OR=12.98, P=0.0019) [8].

Biological context of AKAP9

• We report here a rearrangement of BRAF via paracentric inversion of chromosome 7q resulting in an in-frame fusion between exons 1-8 of the AKAP9 gene and exons 9-18 of BRAF [1].
• Dissociating the centrosomal matrix protein AKAP450 from centrioles impairs centriole duplication and cell cycle progression [9].
• The genomic region containing AKAP350 is found on chromosome 7q21 and is multiply spliced, producing at least three distinct AKAP350 isoforms as well as yotiao, a protein associated with the N-methyl-D-aspartate receptor [10].
• In vitro binding studies confirmed that non- or hypophosphorylated PKC epsilon directly bound to CG-NAP via its catalytic domain, whereas sufficiently phosphorylated PKC epsilon did not [11].
• We propose that AKAP350 is responsible for sequestration of TACC4 to the centrosome in interphase, whereas a separate TACC4 domain results in functional localization of TACC4 to the spindle apparatus in mitotic cells [12].

Anatomical context of AKAP9

• Consistent with a general involvement in postsynaptic structure, yotiao was also found to be specifically concentrated at the neuromuscular junction in skeletal muscle [13].
• Yotiao mRNA (11 kb) is present modestly in brain and abundantly in skeletal muscle and pancreas [13].
• On Western blots, yotiao appears as an approximately 230 kDa band that is present in cerebral cortex, hippocampus, and cerebellum [13].
• AKAP350 can scaffold a number of protein kinases and phosphatases at the centrosome and the Golgi apparatus [3].
• These results imply that CG-NAP and kendrin provide sites for microtubule nucleation in the mammalian centrosome by anchoring gamma-TuRC [14].

Associations of AKAP9 with chemical compounds

• Thus yotiao is an NR1-binding protein potentially involved in cytoskeletal attachment of NMDA receptors [13].
• AKAP350 and CLIC5B association with Golgi elements was lost following brefeldin A treatment [3].
• In polarized Madin-Darby canine kidney cells, AKAP350 localized asymmetrically to one pole of the centrosome, and nocodazole did not alter its localization [10].
• This included treatment of cells with cAMP analogs, inclusion of phosphatase inhibitors or purified PKA in the pipette filling solution, co-expression of catalytically active PKA, expression of the NR1 PKA-site phosphorylation site mimic (S897D) or by co-expression of the PKA scaffolding protein yotiao or the dopamine D(1) receptor [15].
• RESULTS AND CONCLUSIONS: For target coverage, the volume receiving more than 95% of the prescribed dose ranged from 77% (OTP) to 91% (Eclipse and Pinnacle), the volume receiving more than 107% ranged from 3.3% (Hyperion) to 23.2% (OTP) [16].

Physical interactions of AKAP9

• All CLIC family members were able to bind a 133-amino acid domain within AKAP350 through the last 120 amino acids in the conserved CLIC carboxyl termini [3].
• Transforming acidic coiled-coil-containing protein 4 interacts with centrosomal AKAP350 and the mitotic spindle apparatus [12].

Co-localisations of AKAP9

• CLIC4 is enriched at cell-cell junctions and colocalizes with AKAP350 at the centrosome and midbody of cultured mammalian cells [17].

Regulatory relationships of AKAP9

• CG-NAP/D interacted with exogenously expressed cyclin E, which co-localized at centrosomes [18].
• RNA interference for AKAP350 also induced an increase in cdc42 activity during microtubule regrowth [19].

Other interactions of AKAP9

• A giant coiled-coil protein, CG-NAP (centrosome and Golgi localized PKN-associated protein), was localized to the centrosome via the carboxyl-terminal region [14].
• Furthermore, centrosome fractions prepared from cells expressing CG-NAP/D contained increased amount of cdk2 compared with those from control cells [18].
• Centrosome-targeting region of CG-NAP causes centrosome amplification by recruiting cyclin E-cdk2 complex [18].
• The immunoprecipitates of CG-NAP/D exhibited histone H1 kinase activity, suggesting the co-immunoprecipitation of active cyclin-cdk complexes [18].
• The amplified centrosomes co-localized with centrosome markers gamma-tubulin, centrin-2 and kendrin as well as endogenous CG-NAP [18].

Analytical, diagnostic and therapeutic context of AKAP9

• We also evaluated the expression of AKAP9 protein by immunohistochemistry [2].
• T cell locomotion triggered by LFA-1 ligation induces redistribution of CG-NAP/AKAP450 along microtubules in trailing cell extensions [20].
• Immunofluorescence microscopy demonstrated that AKAP350 was associated with centrosomes in many cell types [10].

References