Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation.
|Abstract||Splicing requires reversible phosphorylation of serine/arginine-rich (SR) proteins, which direct splice site selection in eukaryotic mRNA. These phosphorylation events are dependent on SR protein (SRPK) and cdc2-like kinase (CLK) families. SRPK1 phosphorylation of splicing factors is restricted by a specific docking interaction whereas CLK activity is less constrained. To understand functional differences between splicing factor targeting kinases ... [truncated at 450 characters in length]|
|Author||Bullock, Alex N; Das, Sanjan; Debreczeni, Judit E; et al|
|Subject||Amino Acid Sequence Binding Sites Humans Models, Molecular Molecular Sequence Data Mutagenesis, Insertional Nuclear Proteins Phosphorylation Protein Conformation Protein Structure, Tertiary Protein-Serine-Threonine Kinases Protein-Tyrosine Kinases RNA Splicing RNA-Binding Proteins Substrate Specificity chemistry metabolism chemistry metabolism chemistry metabolism chemistry metabolism|
SH2 domains: modulators of nonreceptor tyrosine kinase activity.
|Abstract||The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members ... [truncated at 450 characters in length]|
|Author||Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan;|
|Subject||Disease Enzyme Activation Enzyme Stability Humans Mutation Protein-Tyrosine Kinases src Homology Domains genetics chemistry genetics metabolism|
Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing.
|Abstract||There is a growing recognition of the importance of protein kinases in the control of alternative splicing. To define the underlying regulatory mechanisms, highly selective inhibitors are needed. Here, we report the discovery and characterization of the dichloroindolyl enaminonitrile KH-CB19, a potent and highly specific inhibitor of the CDC2-like kinase isoforms 1 and 4 (CLK1/CLK4). Cocrystal structures of KH-CB19 with CLK1 and CLK3 revealed a n ... [truncated at 450 characters in length]|
|Author||Fedorov, Oleg; Huber, Kilian; Eisenreich, Andreas; et al|
|Subject||Alternative Splicing Catalytic Domain Endothelial Cells Heterocyclic Compounds, 2-Ring Humans Models, Molecular Nitriles Phosphorylation Protein Kinase Inhibitors Protein-Serine-Threonine Kinases Protein-Tyrosine Kinases RNA, Messenger RNA-Binding Proteins Substrate Specificity Thromboplastin drug effects drug effects metabolism chemical synthesis chemistry pharmacology chemical synthesis chemistry pharmacology drug effects chemical synthesis chemistry pharmacology antagonists and inhibitors chemistry metabolism antagonists and inhibitors chemistry metabolism genetics metabolism genetics|
Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class.
|Abstract||ABL2 (also known as ARG (ABL related gene)) is closely related to the well-studied Abelson kinase cABL. ABL2 is involved in human neoplastic diseases and is deregulated in solid tumors. Oncogenic gene translocations occur in acute leukemia. So far no structural information for ABL2 has been reported. To elucidate structural determinants for inhibitor interaction, we determined the cocrystal structure of ABL2 with the oncology drug imatinib. Inter ... [truncated at 450 characters in length]|
|Author||Salah, Eidarus; Ugochukwu, Emilie; Barr, Alastair J; et al|
|Subject||Amino Acid Motifs Crystallography, X-Ray Humans Models, Molecular Piperazines Protein Binding Protein Kinase Inhibitors Protein Structure, Tertiary Protein-Tyrosine Kinases Pyrimidines Triazoles metabolism chemistry metabolism pharmacology antagonists and inhibitors chemistry metabolism metabolism chemistry metabolism pharmacology|