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quantity so as to carry certain information. In the case of sound signal transmission by FM (frequency
modulation) modulation, electromagnetic wave carries sound information that is coded into its frequency,
for instance. Accordingly one can specify the process of signaling by accounting for 'what information
the carrier carries' and 'what the information is coded into'.
The process of signaling carries two kinds of information on 'how to cause a signaling pathway' and
on 'how to orient a signaling pathway' [7]. The former information is coded into 'activity', which is
reified as 'phosphorylation activity' and 'binding activity', for instance. The latter information is coded
into 'molecular recognition', which is reified as 'substrate-enzyme recognition' and 'MH2-MH2 domain
recognition' for instance. Accordingly, CSNO defines 'the process of signaling ' as 'the transmission of
activity through molecular recognition '.
Activity is a physical quantity in reaction kinetics indicating the efficiency of a reactant in causing a
target reaction [6]. Activity is regarded as an abstraction of a functional change from inactivated state
to activated state of a target molecule. For example, an ontological description of 'transmission of
activity to a target molecule' is comparable to a natural description of 'activation of a target molecule'.
Abstraction of the common essence is in need of specification, so that every reaction can be founded on
that in its representation. In contrast, molecular recognition is a common concept in biology, because the
conceptualization has been needed for standardization of common sequence motifs required in molecular
recognition .
Ontological Specification of two Roles Carried by Reactants in Signaling Pathways
CSNO defines two roles that a reactant plays in signaling pathways [6, 7]. One role is of transmitting
activity through molecular recognition. The other role is of constituting a cellular entity in order to keep
its structure and location in a cell. When reactants belong to a complex, the former role is assigned to the
individual components, whereas the latter role is assigned to the complex as a whole. Accordingly, one
ought to focus not on a complex as a structural object but on components carrying molecular recognition
and activity in representation of signaling pathways. Only if molecular recognition is carried by a
complex as a whole, the complex ought to be focused. Such a case is found in molecular recognition
between a transporter and a transported complex in signaling pathways.
RESULTS
Definitions of Units of Petri Nets on the Basis of CSNO
Ontological explication of the process of signaling enables us to specify Petri net units (Table 1), which
standardize Petri net representation. Each unit coincides with a unit of the process of signaling . Places
are associated with reactants holding activity and molecular recognition . Transitions are associated
with reactions transmitting activity. Tokens are associated with the concentration of reactants holding
activity and molecular recognition . The four units in Table 1 are disjoint and cover all the reactions in
signaling pathways, as is indicated in is-a conceptual hierarchy for signaling reactions in Fig. 1(A). The
primary classification is productive reaction or regulatory reaction, in which topological connections of
nodes in the units are different. The classification accounts for the productivity of the reactions. While
productive reactions can produce products reiteratively, regulatory reactions can produce products only
once. The difference is indicated by an additional backward arc from a transition to a place associated
with a reactant playing a catalyst.
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