Mechanisms and significance of polyamine stimulation of various protein kinase reactions

Khalil Ahmed, Said A. Goueli, H. Guy Williams-Ashman

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An overview of the work on polyamine effects on certain protein kinase reactions is presented. In general, the reactions catalyzed by the messenger-independent protein kinases but not by cyclic nucleotide-, Ca2+-, Ca2+-calmodulin-, and Ca2+-anionic lipid-dependent protein kinases, are markedly enhanced by polyamines. The extent of this stimulation depends critically on the nature of the protein substrate and several other factors. A variety of other polycationic compounds including Co3+(NH3)6, polybrene, and certain aminoglycoside antibiotics exert polyamine-like effects in the same reactions. These observations suggest that the charge properties rather than any strict chemical structure play a role in the action of polyamines. Available data do not support a specific "cofactor" function of these amines for the protein kinases involved in the polyamine-stimulable reactions. It appears that the action of polyamines is mediated via their influence on the conformational status of the protein substrates thereby altering the availability of the phosphorylatable sites to the active sites on the protein kinases. Although this notion is supported by several lines of evidence, at present a role of the influence of polyamines on both the substrate and enzyme cannot be ruled out. Possible physiological relevance of the polyamine-stimulable protein kinase reactions observed in the in vitro experiments remains problematic in the absence of precise knowledge on the "effective" or free concentrations of intracellular polyamines.

Original languageEnglish (US)
Pages (from-to)401-421
Number of pages21
JournalAdvances in Enzyme Regulation
Issue numberC
StatePublished - 1986

Bibliographical note

Funding Information:
We are deeplyg ratefutl o Dr. Jerome Seidenfeldo f the Departmenotf Pharmacologayn d the Cancer Center,N orthwesterUnn iversityM edical School,C hicago,I llinois for performinegs timationosf polyamineisn acid-solublee xtractso f prostatec hromatinp reparationTs.h e assistancoef Mr. Alan T. Davis and Ms. CamilleL . Quaglioin thep reparatioonf this reviewis gratefullya cknowledgedT.h e original investigationbsy the authorsa re supporteidn part by U.S.P.H.S. ResearchG rantC A-15062a wardedb y the NationalC ancerI nstituteD, epartmenotf Healtha ndH umanS ervicesa, nd the U.S. VeteransA dministratioMne dicalR esearchF und.


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