High impact information on AKAP11

• Screening of a PMA-stimulated Jurkat cell library identified two additional known AKAPs, AKAP220 and AKAP-KL, and one novel AKAP, myeloid translocation gene 16 (MTG16b) [1].
• Calyculin A, a protein phosphatase inhibitor, also inhibited the activity of GSK-3beta bound to AKAP220 more strongly than the total GSK-3beta activity [2].
• When COS cells were treated with dibutyryl cyclic AMP to activate PKA, the activity of GSK-3beta bound to AKAP220 decreased more markedly than the total GSK-3beta activity [2].
• Cyclic AMP-dependent protein kinase (PKA) and type 1 protein phosphatase (PP1) were also detected in this complex, suggesting that AKAP220, GSK-3beta, PKA, and PP1 form a quaternary complex [2].
• Intermolecular interactions within the AKAP220 signaling complex further contribute to PP1 inhibition as addition of the PKA regulatory subunit (RII) enhances phosphatase inhibition [3].

Biological context of AKAP11

• We previously reported that a 220-kDa A-kinase anchoring protein (AKAP220) coordinates the location of the cAMP-dependent protein kinase (PKA) and the type 1 protein phosphatase catalytic subunit (PP1c) (Schillace, R. V., and Scott, J. D. (1999) Curr. Biol. 9, 321-324) [3].
• Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis [4].
• The hAKAP220 amino acid sequence revealed high similarity to rat AKAP220 in the 1167 C-terminal residues, but contained 727 residues in the N-terminus not present in the reported rat AKAP220 sequence [4].
• Using a combination of protein kinase A type II overlay screening, rapid amplification of cDNA ends, and database searches, a contig of 9923 bp was assembled and characterized in which the open reading frame encoded a 1901-amino-acid A-kinase-anchoring protein (AKAP) with an apparent SDS-PAGE mobility of 220 kDa, named human AKAP220 (hAKAP220) [4].
• Since AKAP220 plays a role in regulating the Rb pathway, its dysregulation may contribute significantly to alterations in cell cycle regulation that facilitate progression of OPLs [5].

Anatomical context of AKAP11

• Immunoprecipitation of AKAP 220 from rat testis extracts resulted in co-purification of the type II PKA holoenzyme [6].
• Immunohistochemical analysis of rat testicular TM4 cells showed that AKAP 220 and a proportion of RII were co-localized in microbodies that appear to be a subset of peroxisomes [6].
• The hAKAP220 protein was present in human male germ cells and mature sperm [4].
• The hAKAP220 mRNA was expressed at high levels in human testis and in isolated human pachytene spermatocytes and round spermatids [4].
• The hAKAP220 protein together with a fraction of PKA types I and II and protein phosphatase I was resistant to detergent extraction of sperm tails, suggesting an association with cytoskeletal structures [4].

Regulatory relationships of AKAP11

• Analysis of truncated PP1c and chimeric PP1/2A catalytic subunits suggests that AKAP220 inhibits the phosphatase in a manner distinct from all known PP1 inhibitors and toxins [3].

Other interactions of AKAP11

• These experiments indicate that regulation of PP1 activity by AKAP220 involves a complex network of intra- and intermolecular interactions [3].

Analytical, diagnostic and therapeutic context of AKAP11

• AKAP220 co-purified with PP1c by affinity chromatography on microcystin sepharos Immunocytochemical analysis demonstrated that the kinase, the phosphatase and the anchoring protein had distinct but overlapping staining patterns in rat hippocampal neurons [7].

References