43. The platelet-derived growth factor (PDGF) is a dimer consisting of two identical polypeptides. On binding to its cell surface receptor.it induces dimerization of the receptor by binding to two receptor molecules. If the intracellular C-terminal domain of the receptor is truncated, which one of the following is most likely to occur?
(1) Both ligand binding and receptor dimerization will be hampered.
(2) Ligand binding will take place followed by consequent signal transduction.
(3) Ligand binding will be hampered.
(4) Ligand binding will take place but no downstream signaling will be triggered.

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Introduction

Platelet-derived growth factor (PDGF) receptors are receptor tyrosine kinases that play essential roles in cellular processes such as proliferation, migration, and differentiation. PDGFs are dimeric ligands that induce receptor dimerization upon binding, which is required for receptor activation and signal transduction.

Structure and Activation of PDGF Receptors

• The receptor’s extracellular domains contain specific ligand-binding sites.

• Ligand binding induces dimerization of two PDGF receptors.

• Dimerization aligns intracellular kinase domains, triggering autophosphorylation primarily in the cytoplasmic C-terminal domains.

• Autophosphorylation creates docking sites for downstream signaling proteins containing SH2 domains.

Effect of C-Terminal Truncation

• Truncation of the cytoplasmic C-terminal domain:

  • Does not affect ligand binding because ligand-binding sites are in the extracellular immunoglobulin-like domains.

  • Does not prevent receptor dimerization since dimerization is stabilized by extracellular and transmembrane regions.

  • Impairs intracellular autophosphorylation and downstream signaling because critical phosphorylation sites and interaction motifs reside in the C-terminal tail.

Literature Evidence

Studies show that even with truncated C-terminal domains, PDGF receptors can still bind ligand and dimerize but fail to effectively initiate downstream signaling cascades due to lack of autophosphorylation sites necessary for recruiting signaling molecules.

Conclusion

The most likely outcome of truncating the intracellular C-terminal domain of PDGF receptors is:

(4) Ligand binding will take place but no downstream signaling will be triggered.

Because ligand binding and dimerization depend largely on the extracellular and transmembrane parts of the receptor, they remain intact, but signaling fails without the intracellular phosphorylation sites.

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