Page 30 - Cell biology PDC 2024
P. 30
gamma subunits remaining attached by their anchor, and the activated
alpha subunit, now bound to a GTP molecule, is freed from the
intracellular wall of the plasma membrane
The beta-gamma dimer as well as the alpha-GTP can propagate an
intracellular signaling cascade
In cAMP-dependent pathway, the activated Gs alpha subunit binds to
and activates an enzyme called adenylyl cyclase that catalyzes the
conversion of ATP into (cAMP)
When the concentration of the second messenger cAMP increases,
activation of an enzyme called protein kinase A (PKA) occurs. The PKA
enzyme is called cAMP-dependent enzyme because it is activated only if
cAMP is present. The activation of cAMP pathway leads to the increase
in heart rate, cortisol secretion, and breakdown of glycogen and fat
After the signal transduction ends, the Gα-GTPase hydrolyze the bound
GTP (Gα-GTP) to GDP and Pi and inactivate the G protein complex by re-
associating the Gα with Gβγ. In this state again GDP is bound to Gα (Gα-
GDP) in the G protein complex. Thus inactivation of the cycle
Ex: TSH receptors and its ligand thyrotropin hormone
If cAMP-dependent pathway is not controlled, it can ultimately lead to
hyper-proliferation, which may contribute to the development and/or
progression of cancer
Alterations in number, structure or function of receptors will lead to
disorder in cellular signal transduction, Up-regulation/hypersensitivity
Down-regulation/desensitization and Receptor Gene Mutation. Ex:
Mutation in TSHR gene (chromosome 14q31) lead to the hyperactivation
of cAMP pathway that results in hyperactivation of the gland and
development of tumor may occur
۲۹