Structural highlights
Function
KAP2_HUMAN Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.
Publication Abstract from PubMed
AML1-ETO is the chimeric protein product of t(8;21) in acute myeloid leukemia. The ETO portion of the fusion protein includes the nervy homology region (NHR) 3 domain, which shares homology with A-kinase anchoring proteins and interacts with the regulatory subunit of type II cAMP-dependent protein kinase A (PKA(RIIalpha)). We determined the solution structure of a complex between the AML1-ETO NHR3 domain and PKA(RIIalpha). Based on this structure, a key residue in AML1-ETO for PKA(RIIalpha) association was mutated. This mutation did not disrupt AML1-ETO's ability to enhance the clonogenic capacity of primary mouse bone marrow cells or its ability to repress proliferation or granulocyte differentiation. Introduction of the mutation into AML1-ETO had minimal impact on in vivo leukemogenesis. Therefore, the NHR3-PKA(RIIalpha) protein interaction does not appear to significantly contribute to AML1-ETO's ability to induce leukemia.
Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity.,Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Corpora T, Roudaia L, Oo ZM, Chen W, Manuylova E, Cai X, Chen MJ, Cierpicki T, Speck NA, Bushweller JH. Structure of the AML1-ETO NHR3-PKA(RIIalpha) complex and its contribution to AML1-ETO activity. J Mol Biol. 2010 Sep 24;402(3):560-77. Epub 2010 Aug 11. PMID:20708017 doi:10.1016/j.jmb.2010.08.007
