© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey A protein interaction network for ErbB receptors  ErbB receptors serve variety of functions  Cell growth  Adhesion  Migration  Apoptosis (programmed cell death)  Some receptors involved in cancer  Harvard University group set out to understand impact of ErbB receptors at system-level

© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey Using protein arrays to set network parameters Reprinted by permission from Macmillan Publishers Ltd: Nature. From Figure 1 in Jones, R. B. et al. (2005) “A quantitative protein interaction network for the ErbB receptors using protein microarrays” Nature 439:

© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey An example of protein interaction network Reprinted by permission from Macmillan Publishers Ltd: Nature. From Figure 2 in Jones, R. B. et al. (2005) “A quantitative protein interaction network for the ErbB receptors using protein microarrays” Nature 439: >2  M 1.5  M 1M1M 500nM <100nM 2M2M KDKD

© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey A systems-level view of ErbB networks  Protein interaction network for ErbB3 does not change significantly over K D values  However EGFR (ErbB1) and ErbB2 become markedly more promiscuous as K D levels increase  EGFR and ErbB2 implicated in cancer Reprinted by permission from Macmillan Publishers Ltd: Nature. From Figure 4 in Jones, R. B. et al. (2005) “A quantitative protein interaction network for the ErbB receptors using protein microarrays” Nature 439: K D <500nMK D <2000nMK D <1500nMK D <1000nM