Control mechanism of JAK/STAT signal transduction pathway.
Suppressor of cytokine signaling-1 (SOCS1) was identified as the negative regulator of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signal transduction pathway. However, the kinetics and control mechanism of the pathway have not yet been fully understood. We have developed the computer simulation of the JAK/STAT pathway. Without nuclear phosphatase, SOCS1's binding to JAK did not cause the decrease in nuclear phosphorylated STAT1. However, without SH2 domain-containing tyrosine phosphatase 2 (SHP-2) or cytoplasmic phosphatase, it did. So nuclear phosphatase is considered to be the most important in this system. By changing parameters of the model, dynamical characteristics and control mechanism were investigated.
Yamada
Satoshi
S
Advanced Technology R&D Center, Mitsubishi Electric Corporation, 8-1-1, Tsukaguchi-Honmachi, Amagasaki, Hyogo 661-8661, Japan. yamada.satoshi@wrc.melco.co.jp
Shiono
Satoru
S
Joo
Akiko
A
Yoshimura
Akihiko
A
D002352:Carrier Proteins / Q000378:metabolism*; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012097:Repressor Proteins; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D050794:STAT1 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases