Biology Reference
In-Depth Information
It is possible, to be sure that an interaction is really relevant,
to confirm that it occurs
in vivo
in its original cellular context, so
as to leave aside interactions which are only detected
in vitro
(Krause
et al
., 2004). This strategy is also biased. We are no longer
measuring the intrinsic capacity of the protein to form bonds due
to its physical structure but rather the bonds that occur in a par-
ticular context. Other factors present in the cell, such as molecular
cofactors or the structure of the cell, always influence the spectrum
of bonds detected
in vivo
, by promoting some interactions and
forbidding others.
The concept of specificity therefore leads to underestimating
the physical interaction possibilities of biological molecules because
it does not encompass the quantitative and continuous aspects of
this phenomenon.
4.3 The consequence of molecular non-specificity:
Return to holism
4.3.1
The network won't work
We thought we could explain mechanisms of regulation by linear
cascades of clearly defined molecular interactions, but molecular
non-specificity makes them a lot more difficult to understand. We
come up against the fact that interaction cascades are intercon-
nected one with another. Two specific examples illustrate this
problem.
The first shows how a signal can activate several different cas-
cades which diverge. The Ras protein plays a major role in con-
trolling cell multiplication and also influences other processes such
as differentiation and apoptosis. It acts as a relay in the transfer of
various extracellular signals such as growth factors, cytokines and
hormones. A linear interaction cascade was first characterised which,
from the cell membrane to the nucleus, successively involved
the protein Raf and a series of kinases, ending in activating the
transcription factor, Elk-1. The causal chain explaining the role of
Ras in cell multiplication was believed to have been elucidated.
