Em. Fykse et al., PHOSPHORYLATION OF RABPHILIN-3A BY CA2+ CALMODULIN-DEPENDENT AND CAMP-DEPENDENT PROTEIN-KINASES IN-VITRO/, The Journal of neuroscience, 15(3), 1995, pp. 2385-2395
Regulation of neurotransmitter release is thought to involve modulatio
n of the release probability by protein; phosphorylation. In order to
identify novel targets for such regulatory processes, we have studied
the phosphorylation of rabphilin-3A in vitro. Rabphilin-3A is a synapt
ic vesicle protein that interacts with rab3A in a GTP-dependent manner
and binds Ca2+ in a phospholipid-dependent manner. Here we show that
rabphilin-3A is an efficient substrate for Ca2+/calmodulin-dependent p
rotein kinase II, which phosphorylates rat rabphilin-3A at residue 234
and 274, and for cAMP-dependent protein kinase, which phosphorylates
rat rabphilin-3A at residue 234. This identifies the middle region of
rabphilin-3A situated between the N-terminal rab3A-binding sequences a
nd the C-terminal C-2-domains involved in Ca2+/phospholipid binding as
a regulatory domain. Thus, rabphilin-3A is a second phosphoprotein on
synaptic vesicles that, similar to synapsin I, may integrate phosphor
ylation signals from multiple protein kinase signaling pathways in the
cell.