Disease relevance of AKAP13

• Here, we analysed the potential impact of four polymorphic non-conservative amino acid exchanges (Arg494Trp, Lys526Gln, Asn1086Asp and Gly2461Ser) in AKAP13 on familial breast cancer [1].
• The Ht31 cDNA includes the estrogen receptor cofactor Brx and the RhoA GDP/GTP exchange factor proto-lymphoid blast crisis (Lbc) sequences [2].
• Our study directly compares the performance of liquid-based (LBC) and conventional cytology for detecting high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) in high-risk, previously unscreened women [3].
• Kinetic studies of leukemic blast cells (LBC) and erythroblasts were carried out in 20 cases of acute myeloblastic leukemia (AML), and the results were compared with those observed in dividing granulocytic precursors (DGP) and erythroblasts in a control group of 16 normal subjects [4].
• A total of 14 lymphocytic leukemia patients were examined, seven with acute lymphocytic leukemia (ALL), two with adult T-cell leukemia (ATL), two with B-chronic lymphocytic leukemia (CLL), two with chronic myelocytic leukemia in lymphoid blastic crisis (CML-LBC), and one with plasma cell leukemia (PCL) [5].

Psychiatry related information on AKAP13

• At the level of subscales, interpersonal detachment (RD3), low resourcefulness (SD3), low responsibility and blaming (SD1) and shyness with strangers (HA3) were predictors for alexithymia [6].

High impact information on AKAP13

• AKAP-Lbc nucleates a protein kinase D activation scaffold [7].
• We demonstrated that AKAP-Lbc Rho-GEF activity is stimulated by the alpha subunit of the heterotrimeric G protein G12 [8].
• We recently identified a novel anchoring protein, called AKAP-Lbc, which functions as a PKA-targeting protein as well as a guanine nucleotide exchange factor (GEF) for RhoA [8].
• Elevation of the cellular concentration of cAMP activates the PKA holoenzyme anchored to AKAP-Lbc, which phosphorylates the anchoring protein on the serine 1565 [8].
• The HA-3 peptide, VTEPGTAQY (HA-3T), is encoded by the lymphoid blast crisis (Lbc) oncogene [9].

Chemical compound and disease context of AKAP13

• Therapy with vincristine (2 mg i.v. weekly) and prednisolone (100 mg p.o. daily) caused a decrease in fibrinogen levels in nine patients treated for lymphoid blast crisis LBC) of chronic myeloid leukemia (CML) [10].
• 1. Four perchloric acid-soluble fractions (PASFs) from human liver metastases of sigmoid colon carcinoma (LSCC), pancreas carcinoma (LPC), breast carcinoma (LBC) and human normal liver (NL) were subjected to DEAE-cellulose column chromatography and separated into three glycoprotein fractions, respectively [11].

Biological context of AKAP13

• The Ht31 gene was assigned to chromosome 15 (region q24-q25) [2].
• These results suggest that Ht31/Rt31 represent a new type of AKAP, containing both an anchoring and a catalytic domain, which appears to be capable of modulating the activity of an interacting partner [2].
• The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein [9].
• These data indicate that the lbc oncogene encodes a novel product implicated in distinct cellular signal transduction functions [12].
• Activation of AKAP-Lbc occurs in response to agonists that stimulate G proteins coupled receptors linked to the heterotrimeric G protein G12, whereas inactivation occurs through mechanisms that require phosphorylation of AKAP-Lbc by anchored PKA and subsequent recruitment of the regulatory protein 14-3-3 [13].

Anatomical context of AKAP13

• A protein of the predicted size of Ht31 (309 kDa) was detected in human mammary carcinoma and HeLa cells [2].
• Despite the lack of T-cell recognition of HA-3- cells, the Thr-->Met substitution had only a modest effect on peptide binding to HLA-A1 and a minimal impact on recognition by T cells when added exogenously to target cells [9].
• Measurement of RII alpha I3A,I5A interaction with the human thyroid AKAP, Ht 31, by two independent methods suggests that mutation of isoleucines 3 and 5 decreases affinity by at least 6-fold [14].
• Expression of AKAP-Lbc in fibroblasts favors the formation of stress fibers in a Rho-dependent manner [15].
• Utilizing BRET we demonstrate that PKA type II holoenzyme was rendered insensitive to beta-adrenergic receptor stimulation with isoproterenol when anchoring to the plasma membrane of COS-7 cells was disrupted by either using Ht31 peptide or by depletion of membrane cholesterol [16].

Associations of AKAP13 with chemical compounds

• Application of lysophosphatidic acid or selective expression of Galpha(12) enhances cellular AKAP-Lbc activation [15].
• Surface competition assays with increasing concentrations of a competitor peptide covering amino acid residues 493 to 515 of the thyroid anchoring protein Ht31, demonstrated that Ht31, but not a proline-substituted peptide, Ht31-P, competed binding of RIIalpha and RIIbeta to all the AKAPs examined (EC(50)-values from 6 to 360 nM) [17].
• However, Ht31, but not Ht31P, inhibited carbachol- and A23187-stimulated augmentation of secretion from cells preincubated with cholera toxin [18].
• Full-length Lbc cDNA encodes 309kDa huge protein with Ht31 PKA anchoring motif, Dof domain, C1 domain, and coiled-coil structure [19].
• AKAP-Lbc: a molecular scaffold for the integration of cyclic AMP and Rho transduction pathways [13].

Other interactions of AKAP13

• Computer-aided analysis of secondary structure, performed on four RII-anchoring protein sequences (the microtubule-associated protein 2, P150, and two thyroid proteins Ht 21 and Ht 31), has identified common regions of approximately 14 residues which display high probabilities of forming amphipathic helices [20].

Analytical, diagnostic and therapeutic context of AKAP13

• In the present report, using co-immunoprecipitation approaches, we demonstrated that AKAP-Lbc can form homo-oligomers inside cells [21].
• The intracellular localization of P47 in phagosome-like vesicles was confirmed by transmission electron microscopy [22].
• RESULTS: The SP-LBC study group consisted of 352,680 specimens with cytodiagnoses and the CS group included 378,990 specimens [23].
• This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system [24].
• Furthermore, no fimbriae-like structures were observed on P47 detected by scanning electron microscopy or negative staining [22].

References