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molecular processes in cells and their subcompartments is increasing rapidly.
Cells are highly structured, hierarchically organized, open systems. We argue
that contemporary models must take account of spatial heterogeneity, multi-
functionality, and individuality.
Conrad [4] discussed the idea of a seed-germination model of enzyme ac-
tion. This model sought to take account of the multiplicities of interaction that
give rise to enzyme function—the factor complex associated with action. Cou-
pled with this interactional view is the self-assembly paradigm [3], which also
addresses issues of nonprogrammability [2]. Enzymes and other proteins can
be described as a “smart thermodynamic machines” which satisfy a “gluing”
(functorial) role in the information economy of the cell [14]. We exploit these
views by drawing comparisons between enzymes and verbs. This text/dialogical
metaphor also helps refine our view of proteins as context-sensitive information
processing agents [13].
Many proteins display a number of “cognitive” capacities, including
pattern recognition
multifunctionality
handling fuzzy data
memory capacity
signal amplification
integration and crosstalk
context-sensitivity.
Multifunctionality is also a dimension of cognitive capacity. Transcription fac-
tors such as CBP and p300 have multiple functions associated with them, includ-
ing molecule-molecule binding and interactions, enzymatic processes, physical
bridges between various transcription factors and the basal transcriptional ma-
chinery, acting as histone acetyltransferases (HATs)—linking transcription to
chromatin remodeling, and mediating negative and positive crosstalk between
different signaling pathways.
The information-processing nature of eukaryotic intracellular signaling path-
ways illustrates many of these concepts well. In the classical model, a cell-
surface receptor binds an extracellular effector (e.g., hormone, pheromone).
Receptor occupation is transduced into an intracellular signal by activation
of an effector enzyme (e.g., adenylate cyclase, phospholipase) responsible for
synthesis of a secondary messenger (e.g., cyclic AMP, diacylglycerol). The
secondary messenger then promotes activation/inactivation of protein kinases
and/or protein phosphatases. Subsequent changes in the phosphorylation state
of target phosphoproteins (e.g., enzymes, structural elements, transcription fac-
tors) bring about the changes in cellular activity observed in response to the
external signal (see Figure 2.1).
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