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Hello. Welcome to the lecture on
SMAD Phosphorylation
and the TGF-β Pathway.
This is your host Joan Massagué.
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The human genome encodes
about 500 different
protein kinases.
Of these, close to 100 are
tyrosine (tyr) kinases,
of which about half
serve as receptors
for growth factors.
They are transmembrane
tyrosine kinases.
The rest, the majority are
serine/threonine kinases
and only a few of these are in
fact transmembrane receptors.
A majority of these receptors
form a family shown as
a single branch in the
human kinome map and
this family all of its
members serve as receptors
for a very important family of
cytokines which is
the TGFβ family.
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TGFβ is the acronym
for transforming
growth factor beta, a cytokine,
and the founding member of
a large family of factors,
more than 30, encoded in
the human genome.
Factors that play
pivotal roles in many aspects of
embryo development as well as
tissue maintenance
or homeostasis.
TGFβ and its family members are
a paradigm of
multifunctionality in biology.
For example, TGFβ activin and
nodal as well as
the related bone
morphogenetic proteins or
BMPs play very important
roles in laying down
the symmetry axis in
early embryo development.
Anterior-posterior, left-right,
and dorsoventral axis.
Yet, later in development,
these factors can play
important roles in
negatively controlling cell
growth and tissue growth.
The relative of TGFβ,
known as myostatin,
is an important suppressor
of skeletal muscle development.
Mutations that inactivate
the myostatin pathway
give rise to excessive
skeletal tissue mass,
as in for example,
in certain breeds of cattle
developed for this purpose.
The multifunctionality
of these factors
also becomes evident in disease.
For example, TGFβ,
which is normally a
powerful inhibitor of
a number of epithelial tissues
and their growth can become
a strong promoter of epithelial
cancers or carcinomas
especially during
the metastatic phase
the spread of these
tumors to the bone.
As we see in this example,
cancer cells are
acting to destroy
the bone matrix and
TGFβ released from
the bone matrix
can act in turn on the cancer
cells to further promote
their action and the destruction
of the bone through the
outgrowth of metastasis.
How cells respond to
