Protein kinase Mζ

Protein kinase Mζ

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.cite journal |author=Hernandez AI, Blace N, Crary JF, Serrano PA, Leitges M, Libien JM, Weinstein G, Tcherapanov A, Sacktor TC.
title=Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications for the molecular mechanism of memory. |journal=J. Biol. Chem. |volume=278 |issue=41 |pages=40305–16 |year=2003 |url=http://www.jbc.org/cgi/content/full/278/41/40305 |pmid=12857744
doi=10.1074/jbc.M307065200
] 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.cite journal |author=Ling D, Benardo L, Serrano P, Blace N, Kelly M, Crary J, Sacktor T |title=Protein kinase Mzeta is necessary and sufficient for LTP maintenance |journal=Nat. Neurosci. |volume=5 |issue=4 |pages=295–6 |year=2002 |url=http://www.nature.com/neuro/journal/v5/n4/full/nn829.html |pmid=11914719 |doi=10.1038/nn829] cite journal |author=Serrano P, Yao Y, Sacktor T |title=Persistent phosphorylation by protein kinase Mzeta maintains late-phase long-term potentiation |journal=J Neurosci |volume=25 |issue=8 |pages=1979–84 |year=2005 |url=http://0-www.jneurosci.org.library.lausys.georgetown.edu/cgi/content/full/25/8/1979 |pmid=15728837 |doi=10.1523/JNEUROSCI.5132-04.2005] cite journal |author=Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton A, Sacktor T |title=Storage of spatial information by the maintenance mechanism of LTP |journal=Science |volume=313 |issue=5790 |pages=1141–4 |year=2006 |url=http://www.sciencemag.org/cgi/content/full/313/5790/1141 |pmid=16931766 |doi=10.1126/science.1128657] 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.cite journal |author=Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton A, Sacktor T |title=Storage of spatial information by the maintenance mechanism of LTP |journal=Science |volume=313 |issue=5790 |pages=1141–4 |year=2006 |url=http://www.sciencemag.org/cgi/content/full/313/5790/1141 |pmid=16931766 |doi=10.1126/science.1128657] 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.cite journal |author=Shema R, Sacktor T, Dudai Y |title=Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKMζ|journal=Science |volume=317 |issue=5840 |pages=951–3 |year=2007 |url=http://www.sciencemag.org/cgi/content/full/317/5840/951 |pmid=17702943 |doi=10.1126/science.1144334] PKMζ is thus the first molecule shown to be a component of the storage mechanism of long-term memory.

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Slater SJ, Ho C, Stubbs CD |title=The use of fluorescent phorbol esters in studies of protein kinase C-membrane interactions. |journal=Chem. Phys. Lipids |volume=116 |issue= 1-2 |pages= 75–91 |year= 2003 |pmid= 12093536 |doi=
*cite journal | author=Carter CA, Kane CJ |title=Therapeutic potential of natural compounds that regulate the activity of protein kinase C. |journal=Curr. Med. Chem. |volume=11 |issue= 21 |pages= 2883–902 |year= 2005 |pmid= 15544481 |doi=

PBB_Controls
update_page = yes
require_manual_inspection = no
update_protein_box = yes
update_summary = no
update_citations = yes


Wikimedia Foundation. 2010.

Игры ⚽ Нужен реферат?

Look at other dictionaries:

  • Protein kinase D1 — Protein kinase D1, also known as PRKD1, is a human gene.cite web | title = Entrez Gene: PRKD1 protein kinase D1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=5587| accessdate = ] PBB Summary section title …   Wikipedia

  • Protein kinase R — (Eukaryotic translation initiation factor 2 alpha kinase 2) is a protein protecting against viral infections. EIF2AK2 is its human gene.cite web | title = Entrez Gene: EIF2AK2 eukaryotic translation initiation factor 2 alpha kinase 2| url =… …   Wikipedia

  • Protein kinase N1 — Protein kinase N1, also known as PKN1, is a human gene.cite web | title = Entrez Gene: PKN1 protein kinase N1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=5585| accessdate = ] PBB Summary section title …   Wikipedia

  • Protein kinase C — ( PKC , EC number|2.7.11.13) is a family of protein kinases consisting of 10 isozymes.cite journal | author = Mellor H, Parker PJ | title = The extended protein kinase C superfamily | journal = Biochem. J. | volume = 332 ( Pt 2) | issue = | pages …   Wikipedia

  • protein kinase C — sē n any of a group of isoenzymes of protein kinase that modify the conformation and activity of various intracellular proteins by catalyzing the phosphorylation of specific serine or threonine amino acid residues in the polypeptide chains of the …   Medical dictionary

  • protein kinase — n any of a class of allosteric enzymes that possess a catalytic subunit which transfers a phosphate from ATP to one or more amino acid residues (as serine, threonine, or tyrosine) in a protein s side chain resulting in a conformational change… …   Medical dictionary

  • Protein kinase A — In cell biology, Protein kinase A (PKA) refers to a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP dependent protein kinase (EC 2.7.11.11). Protein kinase A has several functions… …   Wikipedia

  • Protein kinase — A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). This class of protein may further be separated into subsets as in the case of protein kinase C PKC alpha, PKC beta,… …   Wikipedia

  • protein kinase C — noun Date: 1981 a protein kinase that catalyzes the phosphorylation of specific serine or threonine amino acid residues …   New Collegiate Dictionary

  • protein kinase A — Cyclic AMP dependent protein kinase …   Dictionary of molecular biology

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”