Idc. Fraser et al., A NOVEL LIPID-ANCHORED A-KINASE ANCHORING PROTEIN FACILITATES CAMP-RESPONSIVE MEMBRANE EVENTS, EMBO journal, 17(8), 1998, pp. 2261-2272
Compartmentalization of protein kinases with substrates is a mechanism
that may promote specificity of intracellular phosphorylation events.
We have cloned a low-molecular weight A-kinase Anchoring Protein, cal
led AKAP18, which targets the cAMP-dependent protein kinase (PKA) to t
he plasma membrane, and permits functional coupling to the L-type calc
ium channel. Membrane anchoring is mediated by the first 10 amino acid
s of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid
-modified through myristoylation and dual palmitoylation, respectively
. Transient transfection of AKAP18 into HEK-293 cells expressing the c
ardiac L-type Ca2+ channel promoted a 34 +/- 9% increase in cAMP-respo
nsive Ca2+ currents. In contrast, a targeting-deficient mutant of AKAP
18 had no effect on Ca2+ currents in response to the application of a
cAMP analog. Further studies demonstrate that AKAP18 facilitates GLP-1
-mediated insulin secretion in a pancreatic beta cell line (RINm5F), s
uggesting that membrane anchoring of the kinase participates in physio
logically relevant cAMP-responsive events that may involve ion channel
activation.