LWBK1006-01 LWW-Govindan-Review November 24, 2011 11:17
Chapter 1•Molecular Biology of Cancer Part 1 15tyrosine kinase is activated by its associated ligand. Increasingly, tyrosine
kinases are an important target for novel therapeutics as well. Examples
of this class of agents already in common use include both imatinib mesy-
late (Gleevec) and gefitinib (Iressa). All of the examples listed above are
receptor tyrosine kinases except for Akt. Akt is a threonine/serine kinase
and a key component of the downstream phosphatidylinositol 3 kinase-
signaling pathway through which many of the tyrosine kinases transmit
their signaling.Answer 1.32. The answer is C.
Receptor tyrosine kinases generally consist of an extracellular binding
domain, a transmembrane domain, and an intracellular kinase domain.
These receptors bind ligands that are usually peptides or proteins. Most
are monomeric with the exception of the insulin-receptor family, which
consists of heterodimers covalently bound by disulfide bonds. Six major
classes exist. Activation of the receptor generally requires phosphoryla-
tion of a tyrosine on the receptor, but the insulin binding to the insulin
receptor is an exception to this rule and activation is generated by an
insulin-induced conformational change. Outside of this, most receptor
tyrosine kinases are activated by oligomerization, which brings intracel-
lular kinase domains into proximity to allow cross-phosphorylation. Lig-
ands generally stimulate oligomerization. Although receptor classes have
been defined by particular ligands, it is accepted that particular receptor
classes may bind more than one class of ligand. A particular ligand may
have different conformational changes in the same receptor, leading to
distinct downstream signal pathway activation.Answer 1.33. The answer is B.
Receptor phosphotyrosine phosphatases (RPTPs) are similar in structure
to receptor tyrosine kinases in that they consist of an extracellular domain,
a single transmembrane domain, and an intracellular catalytic domain
(generally two domains). Although no true ligands for RPTPs have been
described, some RPTPs contain structural repeats that suggest adhesion
molecule recognition. Although RPTPs act as phosphatases, they do not
always function in opposition to tyrosine kinases. Particular phospho-
rylation events can be inhibitory to tyrosine kinases, and activation of
phosphatase activity could then increase tyrosine kinase global activity.Answer 1.34. The answer is C.
The CpG dinucleotides are asymmetrically distributed in human DNA,
with approximately half of the genes containing CpG-rich regions
termed CpG island. Most of these CpG islands are not methylated.
X-chromosome inactivation occurs through CpG island methylation.Answer 1.35. The answer is B.
GTP-binding proteins are well-studied mediators of signal transduction.
They are organized into two main classes: (a) heterotrimeric and (b) Ras-
like. These proteins act like switches and undergo conformational changes