The Philadelphia chromosome t(9;22)(q34;q11) results in a BCR-ABL1 fusion. The ABL1 portion contributes constitutive tyrosine kinase activity. Which domain of ABL1 is responsible for substrate phosphorylation?
- A SH2 domain (phosphotyrosine-binding for substrate recruitment)
- B SH1 domain (catalytic kinase domain performing ATP-mediated tyrosine phosphorylation) ✓
- C SH3 domain (proline-rich sequence binding)
- D Actin-binding domain in the C-terminal region
Explanation
ABL1 is a non-receptor tyrosine kinase. Its SH1 domain (Src Homology 1) is the catalytic kinase domain that transfers the gamma-phosphate from ATP to tyrosine residues on substrate proteins. In native ABL1, the SH3 domain binds the SH2-kinase linker in a cis-autoinhibitory conformation suppressing SH1 activity; BCR fusion disrupts this regulation, producing constitutively active SH1-mediated phosphorylation. The SH2 domain binds phosphotyrosine-containing substrates after phosphorylation but is not itself catalytic. The SH3 domain is regulatory. The actin-binding domain mediates cytoskeletal interaction.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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