A strong advantage of ST numbers is that they provide unique identifiers for signal transductions.

ST Representation of Signaling Pathways

To enhance the exploration of signal transduction in a pathway context, one requires an application that allows the visualization of the signaling process in a pathway map. The current graphic representation of signaling pathway is based on a concept description and lack of a fully understanding mechanism or a common taxonomy. However, according to our classification of signal transduction, it is possible to commonly represent signaling pathways by a "metabolic pathway"-like structure in which the proposed nomenclature of signal transductions as the ST classification system.

Figure 1 shows a ST representation of signaling pathways of IFN-gamma pathways.

Figure 1. ST representation of interferon gamma signaling pathway. The ST number consists of four distinct numbers that classify the signal transduction based on our classification. For example, the signal transduction IFN-Gamma -> IFN-GRJ has the ST number 1.3.3.4, which designates an external event (class 1), binding with non-GF cytokines (subclass 1.3) with IFN GR as receptor (sub subclass 1.3.3). The number 4 designates the fourth transduction in this class.

A strong advantage of ST numbers is that they provide unique identifiers for signal transductions. For example, when comparing the signal transductions of two signaling pathway, the ST number is used to determine if two signal transductions have the same function without the need to understand the multiple and confusing names that can be used for the same signal molecule. Similarly, the multiple names used for signal molecules cause confusion when we try to determine if two signal transductions refer to the same molecule. Extensive synonym lists for signal molecules are essential in a signaling database.

Based on the STCDB classification and nomenclature, graphic signaling pathways are produced (Figure 2).

Figure 2. A part of signal transduction pathways based on the STCDB entries. The whole network graphic representation is available at STCDB web site.

Signaling Pathway Alignment

Signaling pathways are not only interconnected to other pathways in the cell. One of additional perspectives to analyze their interactions and regulations is signaling pathway alignment. Signaling pathway alignment reveals differences in signal transduction flux, conversion and regulation in different species. We present signaling pathways as ST number sequences and exploit the PathAligner system to align them.

By applying the metabolic pathway alignment algorithm, it is possible to align signaling pathways. We extract partial signaling pathways from STCDB and list them below.

PKA::PKA->2.3.3.1->phosphorylase kinase->4.3.11.13->glycogen phosphorylase Apaf1::Apaf-1->3.3.1.1->caspase-9->4.12.8.13->caspase-3->4.12.8.3->Acinus Cam-KK2::CaM-KK->4.1.5.5->PKB->4.1.2.3->caspase-9->4.12.8.13->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.1->NF-kB Cam-KK3::CaM-KK->4.1.5.5->PKB->4.1.2.3->caspase-9->4.12.8.13->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.2->I-kB-alpha CDK5_1::CDK5->4.3.3.3->PAK1->4.1.3.2->LIMK-1->4.3.11.10->cofilin PDK2_2::PDK2->4.1.4.5->PKB->4.1.2.3->caspase-9->4.12.8.13->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.2->I-kB-alpha Lck1::Lck->2.5.1.1->VAV->4.12.2.1->Rac->4.9.1.6->PAK3->4.1.3.4->c-Raf-1 Lck2::Lck->2.5.1.1->VAV->4.12.2.1->Rac->4.9.1.5->p35->4.3.3.3->PAK1->4.1.3.2->LIMK-1->4.3.11.10->cofilin cytochrom2::cytochrome c->3.3.1.1->caspase-9->4.12.8.13->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.2->I-kB-alpha Cam-KK1::CaM-KK->4.1.5.5->PKB->4.1.2.3->caspase-9->4.12.8.13->caspase-3->4.12.8.6->presenilin1 Lck3::Lck->2.5.1.1->VAV->4.12.2.1->Rac->4.9.1.5->p35->4.3.3.3->PAK1->4.1.3.3->MLCK->4.3.11.11->myosin light chain cytochrom1::cytochrome c->3.3.1.1->caspase-9->4.12.8.13->caspase-3->4.12.8.3->Acinus CDK5_2::CDK5->4.3.3.3->PAK1->4.1.3.3->MLCK->4.3.11.11->myosin light chain procaspase-3::procaspase-3->4.12.8.2->caspase-3->4.12.8.3->Acinus caspase-8_1::caspase-8->4.12.8.11->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.1->NF-kB CDK5_3::Cdr2->4.3.4.2->Wee1->4.3.10.1->CDK1->4.3.10.2->cyclin B survivin::survivin->4.12.7.1->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.2->I-kB-alpha caspase-8_2::caspase-8->4.12.8.11->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.2->I-kB-alpha Apaf2::Apaf-1->3.3.1.1->caspase-9->4.12.8.13->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.2->I-kB-alpha PDK2_1::PDK2->4.1.4.5->PKB->4.1.2.3->caspase-9->4.12.8.13->caspase-3->4.12.8.10->MEKK1->4.1.11.3->IKK->4.1.6.1->NF-kB

In order to distinguish these pathways, a temporary name is labeled. That is, each pathway begins with "name::". When we input these pathways to the PathAligner's interface and perform multiple pathway alignment, the alignment result and screenshot, are shown in Figure 3.

Figure 3. The multiple alignment result of the listed signaling pathways.

Calcium Signaling Pathways

Coming soon...

Signal Transduction Nomenclature

STCDB's classification is intended to a recommended nomenclature for signal transductions. We are calling for further collabrotaions with worldwide scientific socities.