Rm. Tombes et Gw. Krystal, IDENTIFICATION OF NOVEL HUMAN TUMOR CELL-SPECIFIC CAMK-II VARIANTS, Biochimica et biophysica acta. Molecular cell research, 1355(3), 1997, pp. 281-292
CaMK-II (the (type II) multifunctional Ca2+/CaM-dependent protein kina
se) has been implicated in diverse neuronal and non-neuronal functions
, including cell growth control. CaMKII expression was evaluated in a
variety of human tumor cell lines using RT-PCR (reverse transcriptase
coupled polymerase chain reaction). PCR primers which flanked the CaMK
-II variable domain were used so that all possible variants of the fou
r mammalian CaMK-II genes (alpha, beta, gamma and delta) could be iden
tified. 8 distinct CaMK-II isozymes were identified from human mammary
tumor and neuroblastoma cell cDNA, each of which represented a varian
t of beta, gamma or delta CaMK-II. They included 2 beta isozymes (beta
(e), beta(e)'), 4 gamma isozymes (gamma(B), gamma(C), gamma(G), gamma(
H)) and 2 delta isozymes (delta(C), delta(E)) This is the first report
of human beta and delta CaMK-II sequences. A panel of human cell type
s was then screened for these CaMK-II isozymes. As expected, cerebral
cortex predominately expressed alpha, beta and delta, CaMK-II. In cont
rast, tumor cells, including those of neuronal origin, expressed an en
tirely different spectrum of CaMK-II isozymes than adult neuronal tiss
ue. Tumor cells of diverse tissue origin uniformly lacked alpha CaMK-I
I and expressed 1-2 beta isozymes, at least 3 gamma isozymes and 1-2 d
elta isozymes. When compared to undifferentiated fibroblasts, beta(e),
beta(e)', gamma(G), and gamma(H) were preferentially expressed in tum
or cells. CaMK-II immunoblots also indicated that neuroblastoma and ma
mmary tumor cells express isozymes of CaMK-II not present in their non
-transformed cell or tissue counterpart. The identification of these n
ew, potential tumor-specific CaMK-II variants supports previous indica
tions that CaMK-II plays a role in growth control. In addition, these
results provide insight into both splice variant switching and variabl
e domain structural similarities among all CaMK-II isozymes.