Chemistry Reference
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constants and the gains of the signaling reactions experimentally in order to reveal
the signal and noise propagation along a stochastic signaling system. Single-mole-
cule imaging techniques provide a unique tool for elucidating the stochastic nature of
signaling molecules at work in living cells.
5.10
Conclusions
In RTK signaling across the plasma membrane, single-molecule imaging has
revealed that the formation of signaling dimers of EGFR was facilitated by a high
rate of association and positive cooperative binding of EGF to predimers of EGFR.
The EGF signal was ampli
ed by the secondary activation of EGFR using a dynamic
interaction between occupied and unoccupied receptor molecules. Signaling com-
plexes of NGFR were formed repeatedly during the immobile phase of NGF/NGFR
dynamics suggesting that signals transduce as packets. These results indicate that cell
signaling is improved at the plasma membrane using dynamic molecular systems.
Also, we provide a theoretical framework to describe how signals and noise are
propagated along stochastic signaling systems in living cells. It has long been
suggested that the plasma membrane is not merely a simple entrance for external
information to pass into cells but is the site where sophisticated signal processing
takes place. Single-molecule imaging is now uncovering the mechanism of signal
processing at the plasma membrane.
References
1 Sako, Y. and Yanagida, T. (2003) Nat. Rev.
Mol. Cell Biol. 4 Suppl, SS1
-
SS5.
2 Wazawa, T. and Ueda, M. (2005) Adv.
Biochem. Eng. Biotechnol. 95,77
-
106.
3 Sako, Y. (2006) Mol. Syst. Biol. doi:10.1038/
msb4100100.
4 Schlessinger, J. (2000) Cell
10 Ichinose, J., Murata, M., Yanagida, T. and
Sako, Y. (2004) Biochem. Biophys. Res.
Comm. 324, 1143
-
1149.
11 Kano, F., Sako, Y. and Tagaya, M. (2000)
et al. Mol. Biol. Cell
3087.
12 Huff, K., End, D. and Gordon, G. (1981)
J. Cell Biol.
11
, 3073
-
225.
5 Burgess, A.W., Cho, H.-S., Eigenbrot, C.
et al. (2003) Molecular Cell
103
, 211
198.
13 Shibata, S.C., Hibino, K., Mashimo, T. et al.
(2006) Biochem. Biophys. Res. Comm.
88
, 189
-
-
552.
6 Chung, J.C., Sciaky, N. and Gross, D.J.
(1997) Biophys. J.
12
, 541
342
,
-
322.
14 Simson, R., Sheets, E.D. and Jacobson, K.
(1995) Biophys. J.
316
-
1102.
7 Klein, P., Mattoon, D., Lemmon, M.A. and
Schlessinger, J. (2004) Proc. Natl. Acad. Sci.
USA
73
, 1089
-
993.
15 Zigmond, S.H. (1977) J. Cell Biol.
69
, 989
-
75
,
934.
8 Teramura, Y., Ichinose, J., Takagi, H. et al.
(2006) EMBO J.
101
, 929
-
616.
16 Fisher, P.R., Merkl, R. and Gerisch, G.
(1989) J. Cell Biol.
606
-
4222.
9 Sako, Y., Minoguchi, S. and Yanagida, T.
(2000) Nature Cell Biol.
25
, 4215
-
108
, 973
-
984.
17 Song, L., Nadkarni, S.M., B
odeker, H.U.,
Beta, C., Bae, A., Franck, C., Rappel, W.-J.,
€
2
, 168
172.
-
