Biomedical Engineering Reference
In-Depth Information
route of signal transduction. Their receptors do not possess any inherent enzymatic
activity, but they are associated with cytoplasmic tyrosine kinases called JAKs.
These are present on the plasma membrane, and once a cytokine binds to its recep-
tor, it activates the JAKs that phosphorylate gene regulatory proteins STATs (Signal
Transducer and Activator of Transcription). Activated STATs migrate to the nuclear
region and control gene expression by binding to the responsive elements, resulting
in modified gene expression. Another way of direct communication is adopted by
serine/threonine kinases, which are similar to receptor tyrosine kinase and directly
activate proteins termed SMADs (Sma and Mad related family protein(s)) by phos-
phorylation. SMADs are proteins capable of controlling gene expression, and this
pathway is often used by the TGF- superfamily
[]
.
1.6.4 Hormone Receptors
Several steroid hormones and thyroid hormones transduce the signals by a signifi-
cantly different mechanism. These hormones often traverse the blood stream associ-
ated with specific carrier proteins to reach their site of action. Being lipid soluble,
they pass through the plasma membrane to reach and bind with specific receptor
proteins in the nuclear region. The altered conformation of receptor proteins, due to
hormone binding, allows them to interact with hormone-responsive elements on the
DNA. The interaction causes a changed pattern of gene expression, either enhancing
or suppressing it. Apart from this classical mechanism, some other pathways involv-
ing cyclic AMP and MAP kinases are responsible for other effects exhibited by these
hormones
[5,6]
.
1.7 Cell-Cell Adhesion and Extracellular Matrix
Cells in a multicellular organism are organized into specific tissues, and the indi-
vidual cells in the tissues are associated with each other as well as the extracellular
matrix. The linkages between the individual cells, called
cell junctions
, are classified
into three major categories based on their physiological role: occluding junctions,
anchoring junctions, and communicating junctions. Occluding junctions include
tight junctions that serve to create an impermeable or semipermeable barrier between
the adjoining epithelial cells. They are barriers to the transportation of material and
control the movement of membrane transport proteins between the apical and basal
layers of epithelia. The second category, anchoring junctions, connect the cytoskel-
etal network of the cell to the adjoining cells and/or the extracellular matrix, help-
ing the tissue to survive any inflicted mechanical stress. These types of junctions are
quite abundant and are further classified as
adherens junctions
,
desmosomes
, and
hemidesmosomes
. The adherens junctions connect the intracellular actin filaments
to other cells or extracellular matrix through cadherin and integrin proteins, respec-
tively. Similarly, desmosomes connect the intermediate filaments from one cell to the
next, and hemidesmosomes are the connection site for the intermediate filaments to
the basal lamina. Gap junctions constitute the communicating type of cell junctions.
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