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are identified and characterized, it is increasingly clear that they
have a fundamental role in phosphatase function and that a
comprehensive catalogue of these proteins is crucial to our
understanding of the varied intracellular functions of their associated
catalytic subunits (83).

Targeting these regulatory subunits or disrupting their interaction
with the catalytic subunit might also represent a feasible means to
treat specific diseases. The potential of this idea was typified in the
large-scale loss of function screen done by MacKeigan and colleagues
(84) This group found that 32% of the phosphatases screened
promoted cell survival, whereas 10 protein phosphatases were
classifies as «cell death phosphatases» (that is, the reduction of their
cellular levels caused resistance to apoptosis-inducing agents), and
can therefore be considered as putative tumour suppressors.

Mass spectrometry-based proteomics has become a powerful tool
to identity the components of multiprotein complexes, and more
recently, several techniques have exploited the use of heavy isotope
tags to compare and quantitate relative protein levels under different
biological conditions. Clearly, mass spectrometry-based approaches
and large-scale functional genomics will be driving forces in this
new era in which protein phosphatases will sit on centre stage with
their protein kinase counterparts.

ACKNOWLEDGMENTS

This work was supported by Cancer Research UK (CRUK),
Direccion General de Investigacion Cientifica y Tecnica (DYGYCYT)
and the Basque Government.

BIBLIOGRAPHY

(1) PAWSON, T. (1994) Introduction: protein kinases. Faseb J. 8: 1112-1113.
(2) MANNING, G.; WHYTE, D. B.; MARTINEZ, R.; HUNTER, T. AND SUDARSANAM, S. (2002)

The protein kinase complement of the human genome. Science. 298: 1912-
1934.
(3) OLSEN, J. V.; BLAGOEV, B.; GNAD, F.; MACEK, B.; KUMAR, C.; MORTENSEN, P. AND
MANN, M. (2006) Global, in vivo, and site-specific phosphorylation dynamics
in signaling networks. Cell. 127: 635-648.

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