Page 73 - Concise Pathology for Exam Preparation ( PDFDrive )

58 SECTION I General Pathology

Q. What are the different signalling mechanisms in cell growth?
Write briefly on receptors and signalling pathways involved in
healing and repair.
Ans. Signalling Mechanisms in Cell Growth
Growth factors (GFs) act by binding to specific receptors, which deliver signals to target
cells. Signalling may be:
1. Autocrine (GFs act on the same cells that secrete them, eg, HGF/SF)
2. Paracrine (GFs act on cells adjacent to the cells that secrete them, eg, produced by macro-
phages and action on fibroblasts)
3. Endocrine (produced by endocrine cells and carried in the blood stream to distant
target cells, eg, hormones)

Receptors and Signalling Pathways
• Binding of a ligand to its receptor triggers a series of intracellular signals that induce
transcription factor activation or repression leading to different cellular events.
• Receptors can be on the surface of the target cells, in the cytoplasm or in the nucleus.
Signal transduction can originate from three types of receptors:
1. Receptors with intrinsic tyrosine kinase activity (Flowchart 3.2): These are dimeric
transmembrane molecules having
(a) An extracellular ligand-binding domain.
(b) Transmembrane region.
(c) A cytoplasmic tail with tyrosine kinase activity.
Ligand binding

Dimerization and phosphorylation of receptor subunits

Activation of the receptor tyrosine kinase

Activation of intracellular proteins like RAS, phosphatidylinositol 3-kinase (PI 3-kinase), phospholipase
Cγ (PLC-γ)

Entry into cell cycle/induction of transcription
FLOWCHART 3.2. Signal transduction mediated by receptors with intrinsic tyrosine kinase
activity.
Example: An important pathway stimulated by Rous sarcoma virus (RAS) activation is the
mitogen-activated protein (MAP) kinase cascade, which is involved in the intracellular
signalling of many growth factors, eg, Insulin, EGF, TGF-a, HGF, PDGF and VEGF.
2. Seven transmembrane G protein–coupled receptors (Flowchart 3.3): Polypeptides con-
taining seven transmembrane a-helical segments (traverse the plasma membrane 7 times).
Examples: Vasopressin, histamine, serotonin, glucagon and chemokines.

Signalling initiated by ligand binding and conformational change in receptors

Receptors associate with intracellular G proteins that contain GDP

Exchange of GTP with GDP resulting in activation of the proteins

Activation of cyclic AMP and inositol 1,4,5 triphosphate, which releases calcium from endoplasmic reticulum
FLOWCHART 3.3. Signal transduction mediated by seven transmembrane G protein–coupled
receptors.

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