A-kinase anchoring protein 13 (AKAP13)

A-kinase anchoring protein 13 (AKAP13) is a large multidomain scaffold protein that functions as a key integrator of cAMP/PKA and small GTPase (RhoA) signaling. It contains ankyrin repeats, a Dbl homology (DH) domain providing guanine nucleotide exchange factor (GEF) activity towards RhoA, a pleckstrin homology (PH) domain, and specific domains for anchoring protein kinase A (PKA) and facilitating protein-protein interactions. AKAP13 coordinates the spatial organization of PKA and other kinases to key cellular compartments, and it mediates GPCR regulation of mTORC1 by scaffolding PKA and mTORC1 to promote inhibitory phosphorylation of Raptor at Ser 791. This function modulates critical processes including cell growth, proliferation, survival, and estrogen receptor signaling. Aberrant expression or function of AKAP13 is associated with cancer progression (notably in breast and lung cancer), cardiac diseases, and possibly inflammation, making it a therapeutically interesting—yet challenging—target.

Other names

BRXLBCAKAP-LbcARHGEF13HT31p47HA-3Ht31c-lbcPRKA13AKAP-13PROTO-LBPROTO-LBCbreast cancer nuclear receptor-binding auxiliary proteinguanine nucleotide exchange factor Lbchuman thyroid-anchoring protein 31lymphoid blast crisis oncogenenon-oncogenic Rho GTPase-specific GTP exchange factorprotein kinase A-anchoring protein 13

Scaffold for PKA-mediated phosphorylation and regulation of mTORC1 (including Raptor Ser 791 phosphorylation, leading to mTORC1 inhibition) Guanine nucleotide exchange factor (GEF) activity for RhoA, promoting conversion of RhoA-GDP to RhoA-GTP, activating Rho-dependent pathways