Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

PROTEIN FUNCTION
155
tyrosine
kinase
subfamily
PDGF
receptor
EGF
receptor
Cdc7
Wee1
MAP kinase
subfamily
KSS1 ERK1
Cdk2
Cdc2
cyclin-dependent
kinase subfamily
(cell-cycle control)
Figure 3–62 An evolutionary tree of
selected protein kinases. A higher
eukaryotic cell contains hundreds of such
enzymes, and the human genome codes
for more than 500. Note that only some of
these, those discussed in this book, are
shown.
Src
Lck
Raf
cyclic-AMPdependent
kinase
cyclic-GMPdependent
kinase
Mos
protein kinase C
TGFβ
receptor
myosin lightchain
kinases
Ca 2+ /calmodulindependent
kinase
receptor serine
kinase subfamily
phosphorylate either a serine or a threonine side chain, and many are organized
into clusters that seem to reflect their function—in transmembrane signal transduction,
intracellular signal amplification, cell-cycle control, and so on.
As a result of the combined MBoC6 activities m3.66/3.58 of protein kinases and protein phosphatases,
the phosphate groups on proteins are continually turning over—being
added and then rapidly removed. Such phosphorylation cycles may seem wasteful,
but they are important in allowing the phosphorylated proteins to switch rapidly
from one state to another: the more rapid the cycle, the faster a population of
protein molecules can change its state of phosphorylation in response to a sudden
change in its phosphorylation rate (see Figure 15–14). The energy required to
drive this phosphorylation cycle is derived from the free energy of ATP hydrolysis,
one molecule of which is consumed for each phosphorylation event.
The Regulation of the Src Protein Kinase Reveals How a Protein
Can Function as a Microprocessor
The hundreds of different protein kinases in a eukaryotic cell are organized into
complex networks of signaling pathways that help to coordinate the cell’s activities,
drive the cell cycle, and relay signals into the cell from the cell’s environment.
Many of the extracellular signals involved need to be both integrated and
amplified by the cell. Individual protein kinases (and other signaling proteins)
serve as input–output devices, or “microprocessors,” in the integration process.
An important part of the input to these signal-processing proteins comes from the
control that is exerted by phosphates added and removed from them by protein
kinases and protein phosphatases, respectively.
The Src family of protein kinases (see Figure 3–10) exhibits such behavior. The
Src protein (pronounced “sarc” and named for the type of tumor, a sarcoma, that
its deregulation can cause) was the first tyrosine kinase to be discovered. It is now
known to be part of a subfamily of nine very similar protein kinases, which are
found only in multicellular animals. As indicated by the evolutionary tree in Figure
3–62, sequence comparisons suggest that tyrosine kinases as a group were
a relatively late innovation that branched off from the serine/threonine kinases,
with the Src subfamily being only one subgroup of the tyrosine kinases created in
this way.
The Src protein and its relatives contain a short N-terminal region that becomes
covalently linked to a strongly hydrophobic fatty acid, which anchors the kinase at
the cytoplasmic face of the plasma membrane. Next along the linear sequence of