37. Activity of Receptor tyrosine kinase is initiated by
(1) Phosphorylation
(2) dephosphorylation
(3) Methylation
(4) Acetylation

Activation of Receptor Tyrosine Kinases (RTKs): Phosphorylation as the Initiating Event

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Introduction

Receptor tyrosine kinases (RTKs) are key cell surface receptors involved in transmitting signals for cell growth, differentiation, metabolism, and survival. Their activation is a tightly controlled process that initiates intracellular signaling pathways by phosphorylation.

Mechanism of RTK Activation

1. Ligand Binding and Dimerization: When growth factors or hormones bind to the extracellular domain of RTKs, this induces the receptors to dimerize (pair up), bringing their intracellular domains into close proximity.

2. Autophosphorylation: Dimerization activates the intrinsic tyrosine kinase domains of the receptors. Each receptor phosphorylates tyrosine residues on its partner’s cytoplasmic tail — a process called trans-autophosphorylation.

3. Signal Propagation: The phosphorylated tyrosines serve as docking sites for intracellular signaling proteins containing SH2 or PTB domains. These recruited proteins further propagate the signal, activating downstream pathways such as Ras-MAPK, PI3K-Akt, and others.

Why Phosphorylation Is the Primary Activation Step

• Phosphorylation changes receptor conformation, increasing kinase activity.

• Creates binding sites for signaling molecules to assemble signaling complexes.

• Essential for signal specificity and amplification.

Evaluation of Options

• (1) Phosphorylation: Correct. Phosphorylation of tyrosine residues initiates RTK activity.

• (2) Dephosphorylation: Incorrect; usually terminates the signal.

• (3) Methylation and (4) Acetylation: These are not mechanisms for RTK activation.

Conclusion

The activity of receptor tyrosine kinases is initiated by phosphorylation triggered through ligand-mediated dimerization and autophosphorylation events.

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