Identification of multifunctional ATP-citrate lyase kinase as the alpha-isoform of glycogen synthase kinase-3.
Multifunctional ATP-citrate lyase kinase (ACLK) exhibits several properties that are similar to glycogen-synthase kinase-3 (GSK-3). The molecular cloning of two distinct mammalian GSK-3 cDNAs and a Drosophila melanogaster (fruitfly) homologue, zeste-white3sgg, has established the existence of a GSK-3 subfamily. A multifunctional protein kinase first identified as an ACLK has recently been shown to exhibit several similarities to the alpha- and beta-forms of GSK-3. Here we have used immunological and biochemical analyses to directly compare these enzymes. Thus purified preparations of ACLK isolated from brain and liver preferentially cross-react with anti-GSK-3 alpha antisera and phosphorylate previously defined substrates of GSK-3 at identical sites. Conversely, both alpha- and beta-forms of GSK-3 phosphorylated ATP-citrate lyase at the same site(s) targeted by ACLK. These, and other similarities, demonstrate ACLK to be identical with, or highly related to, GSK-3 alpha, the implications of which are discussed.
Hughes
K
K
Ludwig Institute for Cancer Research, London, U.K.
Ramakrishna
S
S
Benjamin
W B
WB
Woodgett
J R
JR
D000818:Animals; D016367:Baculoviridae / Q000201:enzymology / Q000235:genetics; D001921:Brain / Q000201:enzymology; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002417:Cattle; D038341:Glycogen Synthase Kinases; D015151:Immunoblotting; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity
D011994:Recombinant Proteins; D011494:Protein Kinases; C032202:ATP-citrate lyase kinase; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases