4equ | pdb_00004equ
Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7
Structural highlights
Disease[STK10_HUMAN] The disease may be caused by mutations affecting the gene represented in this entry.[1] Function[STK10_HUMAN] Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.[2] [3] [4] Publication Abstract from PubMedProtein kinases are key components of most mammalian signal transduction networks and are therapeutically relevant drug targets. Efforts to study protein kinase function would benefit from new technologies that are able to profile kinases in complex proteomes. Here, we describe active site-directed probes for profiling kinases in whole cell extracts and live cells. These probes contain general ligands that stabilize a specific inactive conformation of the ATP-binding sites of protein kinases, as well as trifluoromethylphenyl diazirine and alkyne moieties that allow covalent modification and enrichment of kinases, respectively. A diverse group of serine/threonine and tyrosine kinases were identified as specific targets of these probes in whole cell extracts. In addition, a number of kinase targets were selectively labeled in live cells. Our chemical proteomics approach should be valuable for interrogating protein kinase active sites in physiologically relevant environments. Affinity-Based Probes Based on Type II Kinase Inhibitors.,Ranjitkar P, Perera BG, Swaney DL, Hari SB, Larson ET, Krishnamurty R, Merritt EA, Villen J, Maly DJ J Am Chem Soc. 2012 Nov 6. PMID:23088519[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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