Tyrosine-kinase-dependent recruitment of RGS12 to the N-type calcium channel.
Gamma-aminobutyric acid (GABA)B receptors couple to Go to inhibit N-type calcium channels in embryonic chick dorsal root ganglion neurons. The voltage-independent inhibition, mediated by means of a tyrosine-kinase pathway, is transient and lasts up to 100 seconds. Inhibition of endogenous RGS12, a member of the family of regulators of G-protein signalling, selectively alters the time course of voltage-independent inhibition. The RGS12 protein, in addition to the RGS domain, contains PDZ and PTB domains. Fusion proteins containing the PTB domain of RGS12 alter the rate of termination of the GABA(B) signal, whereas the PDZ or RGS domains of RGS 12 have no observable effects. Using primary dorsal root ganglion neurons in culture, here we show an endogenous agonist-induced tyrosine-kinase-dependent complex of RGS12 and the calcium channel. These results indicate that RGS12 is a multifunctional protein capable of direct interactions through its PTB domain with the tyrosine-phosphorylated calcium channel. Recruitment of RGS proteins to G-protein effectors may represent an additional mechanism for signal termination in G-protein-coupled pathways.
Schiff
M L
ML
Department of Pharmacology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Siderovski
D P
DP
Jordan
J D
JD
Brothers
G
G
Snow
B
B
De Vries
L
L
Ortiz
D F
DF
Diversé-Pierluissi
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction
D020864:Calcium Channels, N-Type; D020710:RGS Proteins; C106375:RGS12 protein, human; D018080:Receptors, GABA-B; D011993:Recombinant Fusion Proteins; C491401:Rgs12 protein, rat; D011505:Protein-Tyrosine Kinases; D002118:Calcium