Control of Signal Transduction Cycles: General Results and Application to the Jak-Stat Pathway

• Beirer Stephan

  Theoretical Biophysics Department, Humboldt Universität Berlin

• Höfer Thomas

  Theoretical Biophysics Department, Humboldt Universität Berlin

書誌事項

タイトル別名

• General Results and Application to the Jak-Stat Pathway

抄録

Signal transduction involves the transitions of proteins between inactive and active states thatcan be achieved by reversible phosphorylation, nucleo-cytoplasmic transport, and other processes.We consider a network of such state transitions governed by first-order kinetics and analyse howthe reactions control the occupancy of the network states. First, a theorem is derived that relatesconcentration control coefficients and occupancy of the network states. Second, it is shown thatthe absolute value of each control coefficient is bounded by unity, so that the network does notexhibit ultrasensitive responses. Third, the signs of certain control coefficients are derived from thenetwork topology. These results are applied to a mathematical model of the Jak/Statl signaling.This pathway has been thought to function as a continuous cycle of cytoplasmic activation, nuclearimport, inactivation and re-export of Statl transcription factors, but the recent discovery of anapparently futile nucleo-cytoplasmic cycle of inactive Stat 1 has yielded a more complex picture.We demonstrate here two consequences of shuttling:(1) homeostasis of unphosphorylated Statl inthe cell nucleus and (2) enhanced stimulus sensitivity of the pathway, and discuss their functional implications.

収録刊行物

• Ｇｅｎｏｍｅ　Ｉｎｆｏｒｍａｔｉｃｓ

  Ｇｅｎｏｍｅ　Ｉｎｆｏｒｍａｔｉｃｓ 17 (1), 152-162, 2006

  日本バイオインフォマティクス学会

キーワード

• Stat pathway
• concentration control coefficient
• summation theorem
• node control
• homeostasis
• sensitivity

詳細情報

• CRID: 1390282679465214336
• NII論文ID: 130003812115
• DOI: 10.11234/gi1990.17.152
• ISSN: 2185842X
• ISSN: 09199454
• 本文言語コード: en
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可