Functions of zinc in signaling, proliferation and differentiation of mammalian cells

  • Detmar Beyersmann
  • Hajo Haase


Zinc is essential for cell proliferation and differentiation, especially for the regulation of DNA synthesis and mitosis. On the molecular level, it is a structural constituent of a great number of proteins, including enzymes of cellular signaling pathways and transcription factors. Zinc homeostasis in eukaryotic cells is controlled on the levels of uptake, intracellular sequestration in zinc storing vesicles (‘zincosomes’), nucleocytoplasmic distribution and elimination. These processes involve the major zinc binding protein metallothionein as a tool for the regulation of the cellular zinc level and the nuclear translocation of zinc in the course of the cell cycle and differentiation. In addition, there is also increasing evidence for a direct signaling function for zinc on all levels of signal transduction. Zinc can modulate cellular signal recognition, second messenger metabolism, protein kinase and protein phosphatase activities, and it may stimulate or inhibit activities of transcription factors, depending on the experimental systems studied. Zinc has been shown to modify specifically the metabolism of cGMP, the activities of protein kinase C and mitogen activated protein kinases, and the activity of transcription factor MTF-1 which controls the transcription of the genes for metallothionein and the zinc transporter ZnT-1. As a conclusion of these observations new hypotheses regarding regulatory functions of zinc ions in cellular signaling pathways are proposed.

Key words

differentiation metallothionein proliferation signal transduction zinc 



Activating transcription factor-2


CREB associated factor


Cyclic adenosine monophosphate


Calcium/calmodulin dependent protein kinase-2


Cyclic guanosine monophosphate


Cyclic AMP response element binding factor


Diethylenetriaminepentaacetic acid


Epidermal growth factor


Extracellular signal-regulated kinase


γ-Aminobutyric acid


Insulin-like growth factor-1




Mitogen activated protein kinase




Metal response element-binding transcription factor-1


N-Methyl-D-aspartic acid


Nitric monoxide


Cyclic nucleotide phosphodiesterase


Phosphatidylinositol 3-kinase


Protein kinase C


N,N,N′,N′-Tetrakis(2-pyridylmethyl) ethylenediamine


Zinc transporter-1


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Copyright information

© Springer Science+Business Media Dordrecht 2001

Authors and Affiliations

  • Detmar Beyersmann
    • 1
  • Hajo Haase
    • 1
  1. 1.Department of Biology and ChemistryUniversity of BremenBremenGermany

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