PubMed:21098038 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/21098038","sourcedb":"PubMed","sourceid":"21098038","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/21098038","text":"Quantitative analysis of ERK2 interactions with substrate proteins: roles for kinase docking domains and activity in determining binding affinity.\nExtracellular signal-regulated kinase-1 and -2 (ERK1/2) proteins regulate a variety of cellular functions, including cell proliferation and differentiation, by interacting with and phosphorylating substrate proteins. Two docking sites, common docking (CD/ED) domain and F-site recruitment site (FRS), on ERK proteins have been identified. Specific interactions with the CD/ED domain and the FRS occur with substrates containing a docking site for ERK and JNK, LXL (DEJL) motif (D-domain) and a docking site for ERK, FXF (DEF) motif (F-site), respectively. However, the relative contributions of the ERK docking sites in mediating substrate interactions that allow efficient phosphate transfer are largely unknown. In these studies, we provide a quantitative analysis of ERK2 interactions with substrates using surface plasmon resonance to measure real time protein-protein interactions. ERK2 interacted with ELK-1 (DEF and DEJL motifs), RSK-1 (DEJL motif), and c-Fos (DEF motif) with K(D) values of 0.25, 0.15, and 0.97 μM, respectively. CD/ED domain mutations inhibited interactions with ELK-1 and RSK-1 by 6-fold but had no effect on interactions with c-Fos. Select mutations in FRS residues differentially inhibited ELK-1 or c-Fos interactions with ERK2 but had little effect on RSK-1 interactions. Mutations in both the ED and FRS docking sites completely inhibited ELK-1 interactions but had no effect on interactions with stathmin, an ERK substrate whose docking site is unknown. The phosphorylation status of ERK2 did not affect interactions with RSK-1 or c-Fos but did inhibit interactions with ELK-1 and stathmin. These studies provide a quantitative evaluation of specific docking domains involved in mediating interactions between ERK2 and protein substrates and define the contributions of these interactions to phosphate transfer.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":146},"obj":"Sentence"},{"id":"T2","span":{"begin":147,"end":363},"obj":"Sentence"},{"id":"T3","span":{"begin":364,"end":485},"obj":"Sentence"},{"id":"T4","span":{"begin":486,"end":702},"obj":"Sentence"},{"id":"T5","span":{"begin":703,"end":860},"obj":"Sentence"},{"id":"T6","span":{"begin":861,"end":1033},"obj":"Sentence"},{"id":"T7","span":{"begin":1034,"end":1184},"obj":"Sentence"},{"id":"T8","span":{"begin":1185,"end":1307},"obj":"Sentence"},{"id":"T9","span":{"begin":1308,"end":1448},"obj":"Sentence"},{"id":"T10","span":{"begin":1449,"end":1632},"obj":"Sentence"},{"id":"T11","span":{"begin":1633,"end":1769},"obj":"Sentence"},{"id":"T12","span":{"begin":1770,"end":1990},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"},{"subj":"T10","pred":"source","obj":"sentences"},{"subj":"T11","pred":"source","obj":"sentences"},{"subj":"T12","pred":"source","obj":"sentences"}]},{"project":"Allie","denotations":[{"id":"SS1_21098038_2_0","span":{"begin":417,"end":440},"obj":"expanded"},{"id":"SS2_21098038_2_0","span":{"begin":442,"end":445},"obj":"abbr"},{"id":"SS1_21098038_3_0","span":{"begin":577,"end":610},"obj":"expanded"},{"id":"SS2_21098038_3_0","span":{"begin":612,"end":616},"obj":"abbr"},{"id":"SS1_21098038_3_1","span":{"begin":641,"end":666},"obj":"expanded"},{"id":"SS2_21098038_3_1","span":{"begin":668,"end":671},"obj":"abbr"}],"relations":[{"id":"AE1_21098038_2_0","pred":"abbreviatedTo","subj":"SS1_21098038_2_0","obj":"SS2_21098038_2_0"},{"id":"AE1_21098038_3_0","pred":"abbreviatedTo","subj":"SS1_21098038_3_0","obj":"SS2_21098038_3_0"},{"id":"AE1_21098038_3_1","pred":"abbreviatedTo","subj":"SS1_21098038_3_1","obj":"SS2_21098038_3_1"}],"attributes":[{"subj":"SS1_21098038_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_21098038_2_0","pred":"source","obj":"Allie"},{"subj":"SS1_21098038_3_0","pred":"source","obj":"Allie"},{"subj":"SS2_21098038_3_0","pred":"source","obj":"Allie"},{"subj":"SS1_21098038_3_1","pred":"source","obj":"Allie"},{"subj":"SS2_21098038_3_1","pred":"source","obj":"Allie"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":147,"end":160},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/GO_0005576"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#9c93ec","default":true},{"id":"Allie","color":"#a4ec93"},{"id":"Anatomy-UBERON","color":"#ec93be"}]}]}}