Chemistry Reference
In-Depth Information
5
Signal Transduction across the Plasma Membrane
Masahiro Ueda, Tatsuo Shibata, and Yasushi Sako
5.1
Introduction
The plasma membrane is the entrance for various extracellular signals into the
cytoplasm. This chapter describes the single-molecule imaging approach toward
understanding signal transduction across the plasma membrane. Because the
plasma membranemakes a good target for single-moleculemicroscopy, the behavior
of cell signaling molecules in the plasma membrane has been studied in living cells
using single-molecule imaging [1
-
3]. This chapter deals with the signaling of
epidermal growth factor receptor (EGFR) in mammalian cells and cAMP receptor
1 (cAR1) in Dictyostelium cells. EGFR and cAR1 belong to the receptor protein
tyrosine kinases (RTKs) and the trimeric G-protein coupled receptor (GPCRs)
superfamilies, respectively. RTKs and GPCRs are two large superfamilies of mem-
brane receptors situated on the plasma membrane which excite complicated reaction
systems inside cells. Analysis of the reaction systems requires quantitative informa-
tion in both time and space. Superior quantitative data with spatiotemporal resolu-
tion in single-molecule imaging measurements is ideal to satisfy this requirement.
Hence, an aim of the studies reported in this chapter is to understand the behavior of
complicated reaction networks inside cells based on unitary protein reactions as
visualized in single molecules.
5.2
Signal Transduction Mediated by Receptor Tyrosine Kinase
RTK is a large super family of membrane receptors found on the cell surface [4]. The
role of most members of the RTKs involves signal transduction for cell proliferation
and differentiation. A typical RTK consists of a single membrane-spanning protein
with a ligand-binding domain at the extracellular side and a tyrosine kinase domain at
the cytoplasmic side. Upon binding with the ligand, the kinase activity of RTK is
