Alzheimer's Disease and Frontotemporal Dementias

A Review with Particular Reference to Pin1 Protein

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Compiled by: Julian Thorpe

Protein Kinase C

Please Note: Due to time constraints, the text part of this page has not been updated for some time. However, references are added reasonably frequently.

Protein kinase C (PKC) is reversibly activated at the plasma membrane with release of intracellular Ca2+. PKC is also irreversibly activated by calpain-mediated PKC cleavage of the regulatory and catalytic subunits. Resultant free PKC catalytic subunits are termed "PKM''. Unlike PKC, PKM is co-factor- independent, remains active following diffusion away from the membrane, and can theoretically phosphorylate targets inaccessible to, and inappropriate for, PKC (from Ekinci and Shea, 1999).

Ekinci and Shea, 1999 examined the downstream consequences of PKC activation on phosphorylation of tau .Their results indicated that PKC phosphorylates tau via the MAP kinase pathway, but that PKM can bypass this requirement, demonstrating that distinct intracellular pathways can be mediated by PKC and PKM.

Some Related References

Cordey, M, Gundimeda, U, Gopalakrishna, R, Pike, CJ (2003) Estrogen activates protein kinase C in neurons: role in neuroprotection. JOURNAL OF NEUROCHEMISTRY 84: 1340-1348

Ekinci, FJ and Shea, TB (1999) Free PKC catalytic subunits (PKM) phosphorylate tau via a pathway distinct from that utilized by intact PKC. BRAIN RESEARCH 850: 207-216

Kuperstein, F, Reiss, N, Koudinova, N and Yavin, E (2001) Biphasic modulation of protein kinase C and enhanced cell toxicity by amyloid beta peptide and anoxia in neuronal cultures. JOURNAL OF NEUROCHEMISTRY 76: 758-767

Ma, WY, Zheng, WH, Belanger, S, Kar, S and Quirion, R (2001) Effects of amyloid peptides on cell viability and expression of neuropeptides in cultured rat dorsal root ganglion neurons: a role for free radicals and protein kinase C. EUROPEAN JOURNAL OF NEUROSCIENCE 13: 1125-1135

Mudher, A, Chapman, S, Richardson, J, Asuni, A, Gibb, G, Pollard, C, Killick, R, Iqbal, T, Raymond, L, Varndell, I, Sheppard, P, Makoff, A, Gower, E, Soden, PE, Lewis, P, Murphy, M, Golde, TE, Rupniak, HT, Anderton, BH and Lovestone, S (2001) Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase. JOURNAL OF NEUROSCIENCE 21: 4987-4995

Yeon, SW, Jung, MW, Ha, MJ, Kim, SU, Huh, K, Savage, MJ, Masliah, E and Mook-Jung, I (2001) Blockade of PKC epsilon activation attenuates phorbol ester-induced increase of alpha-secretase-derived secreted form of amyloid precursor protein. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 280: 782-787