Rg. Panchal et al., DIFFERENTIAL PHOSPHORYLATION OF NEURONAL SUBSTRATES BY CATALYTIC SUBUNITS OF APLYSIA CAMP-DEPENDENT PROTEIN-KINASE WITH ALTERNATIVE N-TERMINI, The Journal of biological chemistry, 269(38), 1994, pp. 23722-23730
cAMP-dependent protein kinase (PKA) is an important participant in neu
ronal modulation: the ability of neurons to change their properties in
response to external stimuli. In Aplysia mechanosensory neurons, PKA
plays roles in both short and long term presynaptic facilitation, whic
h is a simple model for learning and memory. PKA in Aplysia is a colle
ction of structurally and functionally diverse regulatory and catalyti
c (C) subunits. We have argued that this diversity may in part account
for the ability of the enzyme to take part in neuronal events that ar
e spatially and temporally separated. Here, we add credence to this hy
pothesis by showing that C subunits of Aplysia PRA with alternative N
termini target different substrates in subcellular fractions from Aply
sia neurons, despite their similar actions on synthetic peptide substr
ates. Purified recombinant C-APL-A N1A1, which has an N terminus that
is homologous to the myristylated sequence described in mammals, catal
yzes the formation of two phosphoproteins of 24 and 8 kDa more rapidly
than C-APL-A N2A1, which has a distinct N terminus weakly related to
that of the yeast TPK1 gene product. The 24-kDa phosphoprotein, but no
t the 8-kDa species, is detected in taxol-stabilized microtubules, sug
gesting that it is associated with the cytoskeleton. C-APL-A N2A1, in
contrast, generates a 55 kDa phosphoprotein that is not observed with
C-APL-A N1A1. The 55-kDa species is found in the detergent supernatant
of the cytoskeleton fraction. Differential targeting of substrates by
C subunits of PKA may therefore contribute to the ability of this kin
ase to play multiple roles in neuronal modulation.