Protein kinase Mζ

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Protein kinase C, zeta
Identifiers
Symbol(s)	PRKCZ; PKC2
External IDs	OMIM: 176982 MGI: 97602 Homologene: 55681
EC number	2.7.1.37
Gene ontology Molecular Function: • nucleotide binding • protein serine/threonine kinase activity • atypical protein kinase C activity • protein binding • ATP binding • zinc ion binding • transferase activity • diacylglycerol binding • metal ion binding Cellular Component: • membrane fraction • cytoplasm • plasma membrane • tight junction • cell cortex • apical cortex Biological Process: • microtubule cytoskeleton organization and biogenesis • protein amino acid phosphorylation • anti-apoptosis • intracellular signaling cascade
RNA expression pattern
Image:PBB GE PRKCZ 202178 at tn.png More reference expression data
Orthologs
	Human	Mouse
Entrez	5590	18762
Ensembl	ENSG00000067606	ENSMUSG00000029053
Uniprot	Q05513	Q3UHM5
Refseq	NM_001033581 (mRNA) NP_001028753 (protein)	NM_001039079 (mRNA) NP_001034168 (protein)
Location	Chr 1: 1.97 - 2.11 Mb	Chr 4: 154.1 - 154.21 Mb
Pubmed search	[1]	[2]

Protein kinase Mζ (also called PKMζ or PKMzeta) is the independent catalytic domain of protein kinase Cζ and, lacking an autoinhibitory regulatory domain of the full-length PKCζ, is constitutively active. This constitutive or autonomous activity allows the kinase to be independent of second messengers and thus persistently active. It was originally thought of as being a cleavage product of full-length PKCζ, an atypical isoform of protein kinase C (PKC). Like other PKC isoforms, PKCζ is a serine/threonine kinase that adds phosphate groups to target proteins. It is atypical in that unlike other PKC isoforms, PKCζ does not require calcium or diacylglycerol (DAG) to become active, but rather relies on a second messenger other than DAG, presumably generated through a phosphoinositide 3-kinase (PI3-kinase) pathway. It is now known that PKMζ is not the result of cleavage of full-length PKCζ, but rather, in mammalian brain, is translated from its own brain-specific mRNA, that is transcribed from the full-length PKCζ gene.^[1] The promotor for full-length PKCζ is largely inactive in the forebrain and so PKMζ is the dominant form of ζ in the forebrain and the only PKM that is translated from its own mRNA.

PKMζ is thought to be responsible for maintaining the late phase of long-term potentiation.^[1][1][1] This theory arose from the observation that PKMζ perfused postsynaptically into neurons causes synaptic potentiation and selective inhibitors of PKMζ, when bath applied 1 hr after tetanization, inhibit the late phase or maintenance of LTP. Thus PKMζ is both necessary and sufficient for maintaining LTP. Subsequent work showed that inhibiting the kinase reversed LTP maintenance when applied up to 5 hours after LTP was induced in hippocampal slices, and after 22 hr in vivo. Inhibiting PKMζ in behaving animals erased spatial long-term memories in the hippocampus that were up to 1 month-old, without affecting spatial short-term memories.^[1] In the neocortex, thought to be the site of storage for most long-term memories, PKMζ inhibition erased memories for conditioned taste aversion in the insular cortex.^[1] PKMζ is thus the first molecule shown to be a component of the storage mechanism of long-term memory.

References

Further reading

v • d • e Kinases: Serine/threonine-specific protein kinases (primarily EC 2.7.11)
2.7.11	Pyruvate dehydrogenase kinase - Protein kinase A - Protein kinase G - Protein kinase C (Protein kinase Mζ) - Rhodopsin - Beta adrenergic receptor - G-protein coupled receptor kinases - Ca2+/calmodulin-dependent - Myosin light-chain) - Phosphorylase - Cyclin-dependent - Mitogen-activated (Extracellular signal-regulated, C-Jun N-terminal (MAPK8, MAPK9), P38 mitogen-activated protein) - MAP3K - GSK-3 - AMP-activated
2.7.12	MAP2K (1, 2, 3, 4, 5, 6, 7)
2.7.1.37, or unknown	Anti-Mullerian hormone receptor - Ataxia telangiectasia mutated - Aurora (A, B) - Mammalian target of rapamycin - Bone morphogenetic protein receptors (1, 2) - CDKL5 - c-Raf - EIF-2 - Ribosomal s6 - Protein kinase B - PDK1