Table 1.
Overview of selected C kinase anchoring proteins (C-KAPs).
| Protein | Primary functions | Localization | Site of interaction | Effects of interaction | References |
|---|---|---|---|---|---|
| Protein kinase inhibitor peptide (PKI) | Inhibits PKA catalytic activity | Cytoplasm and nucleus | Pseudosubstrate sequence of PKI interacts with the substrate binding sites in the catalytic cleft of the C subunit | Inhibits PKA C phosphorylation PKI contains a NES that assists export of the C subunit out of the nucleus | (107–109, 112–114) |
| Ribosomal S6 kinase1 (RSK1) | Ser/Thre kinase that phosphorylates some of the same targets as PKA | Cytoplasm and nucleus | Cα1 binds to the 13 C-terminal amino acids in Ser732 phosphorylated RSK1 | Inhibits C subunit activity by stimulating the reassociation of the R and C subunits | (135–138) |
| Heat shock factor 1 (HSF1) | Controls heat shock responses Implicated in cancer and neurodegenerative disease | Cytoplasm and nucleus | Not known | Phosporylation by PKA on Ser320 in HSF1 is important for nuclear localization of HSF1 Unknown effects on the C subunit | (139–143) |
| A-kinase interacting protein (AKIP) | Interacts with the p65 subunit of NF-κB Brings the C subunit in close proximity to NFκB for phosphorylation by the C subunit | Nucleus | The C-terminal end of AKIP interacts with the N-terminal α-helix (aa 14–39) of the C subunit | Targets and retains Cα1 in the nucleus | (75, 127, 128) |
| Inhibitor of NF-κB (IκB) | Inhibits NF-κB-dependent transcription by binding to its DNA-binding site | Cytoplasm | Unknown part of IκB binds to the N-terminal end of the C subunit (aa 46–76) | Inhibits C subunit activity by blocking the ATP-binding site cAMP independent mechanism | (127) |
| Heterotrimeric G protein GαO | Heterotrimeric G protein hydrolysing GTP to GDP. Links GPCR to enzymes such as AC and phospholipases. | Cytoplasm | The GTPase domain in GαO interacts with an unknown part of Cα1 | Targets active Cα1 to the cytoplasm | (129) |
| Phoshodiesterase 7A1 (PDE7A1) | Hydrolysis of cAMP to 5′ AMP Targets the C subunit to AKAP CBFA2T3, independent of the R subunit. | Cytoplasm | Two N-terminal pseudosubstrate sequences in PDE7A1 interacts with the C subunit | Inhibits C subunit activity by blocking the substrate binding site | (130–133) |
| Caveolin-1 | Principal components of caveolae membranes and involved in receptor-independent endocytosis Forms a complex with the C subunit to promote phosphorylation of Perilipin | Cytoplasm | Scaffolding and C-terminal domain of Caveolin-1 binds to unknown part of the C subunit | Inhibits C subunit activity | (117–120) |
| Homologous to AKAP95 (HA95) | Regulation of DNA replication, nuclear envelope dynamics and HDAC pathway. | Nucleus | Not known | Targets the C subunit to the nucleus | (147–154) |
| Rab13 | GTPase with regulatory function in epithelial tight junctions | Cytoplasm | Not known | Inhibits C subunit-dependent phosphorylation of VASP in epithelial cells | (115, 116) |
| p73 | Transcription factor that promotes apoptosis and cell cycle arrest | Nucleus | N-terminal (aa 63–130) and C-terminal (aa 469–636) interact with unknown domain of the Cβ1 subunit | C subunit-dependent phoshorylation inhibits transcriptional and proapoptotic activity of p73 | (144, 145) |
| SRSF7 | Several functions in RNA processing, including pre-mRNA splicing | Cytoplasm and nucleus | Not known | Upregulated PKA activity prevents inhibition of tau exon 10 inclusion by SRSF7 | (161) |
| GPKOW | RNA-and protein-binding protein | Nucleus | Not known | C-subunit-dependent phosphorylation of Ser27 and Thr316 inhibit GPKOWs ability to bind total RNA | (162) |
| SRSF1 | Several functions in RNA processing, including pre-mRNA splicing | Cytoplasm and nucleus | Not known | C-subunit-dependent phosphorylation of SRSF1 modulates its effect on splicing | (156, 157) |