Protein interaction domains – SH2 (Src homology 2) domains specifically bind which motif on target proteins?

Introduction:
Modular protein domains decode post-translational modifications to route signals inside cells. SH2 domains are classic readers of tyrosine phosphorylation, linking activated receptors and kinases to downstream effectors. This question tests knowledge of their binding specificity.

Given Data / Assumptions:

• Tyrosine phosphorylation is a key event in receptor tyrosine kinase and cytokine receptor pathways.
• SH2 domains are present in many signaling proteins (e.g., Src, PI3K, Grb2, PLCγ).
• Binding requires both pTyr and surrounding sequence determinants.

Concept / Approach:
SH2 domains recognize phosphotyrosine residues embedded in short motifs, with specificity conferred by residues C-terminal to the pTyr. This enables selective recruitment of SH2-containing proteins to activated receptors or scaffolds, orchestrating pathway assembly and amplification.

Step-by-Step Solution:

Verification / Alternative check:
Mutating the critical tyrosine to phenylalanine (cannot be phosphorylated) abrogates SH2 binding; synthetic pTyr peptides compete for binding, confirming specificity.

Why Other Options Are Wrong:

• Phosphoserine: bound by 14-3-3 proteins or FHA domains, not SH2.
• GDP, Ca2+, ubiquitin: interact with other domain classes (RAS effectors, EF-hands, ubiquitin-binding domains).

Common Pitfalls:
Confusing SH2 with SH3 (proline-rich motif binding) or PTB (phosphotyrosine-binding with different motif rules).

Final Answer:
Phosphorylated tyrosine residues (pTyr) within defined sequence contexts