The Cell - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 23

Extracelluar matrix

Signal molecule

Inactive RAS protein Active RAS protein

GDP

Activated
receptor
tyrosine kinase

GTP Onward transmission of signal

GDP

GTP

RAS activating protein
Adaptor protein

Cytoplasm

Figure 1.10 Signal transduction via enzyme-linked receptors.

residue on the cytosolic side of these proteins. The receptors are usually helical in
structure, and binding with a triggering signal leads to dimer formation by the link-
age of two receptors. The tail regions of the two proteins in the dimer interact with
each other and each phosphorylates the other.
The activated receptors attract several intracellular-signaling proteins like protein
kinase B, phosphatidylinositol -kinase, and others. But the receptor tyrosine kinases
have a separate route of action. Receptor tyrosine kinases activate Ras, a small pro-
tein bound by a lipid tail to the cytoplasmic side of the plasma membrane. The Ras
group of proteins are single-unit monomeric GTP-binding proteins and are similar
to the  subunit of trimeric GTP-binding proteins. The activated Ras phosphorylates
kinase enzymes, which in turn phosphorylate other kinases, passing the signal from
plasma membrane to the nuclear region. The whole relay is called a MAP kinase
cascade because mitogen-activated protein kinase (MAP kinase) is the last kinase in
the series. MAP kinase brings about phosphorlyation of serine and threonine present
on transcription-controlling proteins. The phosphorylation may activate or suppress
activity of the gene ( Fig. 1.10 ). The result may be observed as proliferation, differen-
tiation, and so on.
Ras is a very important protein whose role has been implicated in cancers. In
response to the activation of Ras, the cells respond by growth and proliferation. If
Ras remains activated, then an uncontrolled growth and proliferation are observed.
Some mutation in the Ras gene or other proteins in the pathway often leads to an
uncontrolled outburst of growth, causing cancer [2,] .
The information dissipation through signaling cascades is one way of communi-
cation; there are hormones and local mediators like cytokines that have a differing