Beschreibung:
<jats:p>t‐Darpp (truncated isoform of dopamine‐ and <jats:styled-content style="fixed-case">cAMP</jats:styled-content>‐regulated phosphoprotein) is a protein encoded by the <jats:italic><jats:styled-content style="fixed-case">PPP</jats:styled-content>1R1B</jats:italic> gene and is expressed in breast, colon, esophageal, gastric, and prostate cancers, as well as in normal adult brain striatal cells. Overexpression of t‐Darpp in cultured cells leads to increased protein kinase A activity and increased phosphorylation of <jats:styled-content style="fixed-case">AKT</jats:styled-content> (protein kinase B). In <jats:styled-content style="fixed-case">HER</jats:styled-content>2+ breast cancer cells, t‐Darpp confers resistance to the chemotherapeutic agent trastuzumab. To shed light on t‐Darpp function, we studied its secondary structure, oligomerization status, metal‐binding properties, and phosphorylation by cyclin‐dependent kinases 1 and 5. t‐Darpp exhibits 12% alpha helix, 29% beta strand, 24% beta turn, and 35% random coil structures. It binds calcium, but not other metals commonly found in biological systems. The T39 site, critical for t‐Darpp activation of the <jats:styled-content style="fixed-case">AKT</jats:styled-content> signaling pathway, is a substrate for phosphorylation by cyclin‐dependent kinase 1 and cyclin‐dependent kinase 5. Gel filtration chromatography, sedimentation equilibrium analysis, blue native gel electrophoresis, and glutaraldehyde‐mediated cross‐linking experiments demonstrate that the majority of t‐Darpp exists as a monomer, but forms low levels (< 3%) of hetero‐oligomers with its longer isoform Darpp‐32. t‐Darpp has a large Stokes radius of 4.4 nm relative to its mass of 19 kDa, indicating that it has an elongated structure.</jats:p>