title: A novel interaction between the SH2 domain of signaling adaptor protein Nck-1 and the upstream regulator of the Rho family GTPase Rac1 engulfment and cell motility 1 (ELMO1) promotes Rac1 activation and cell motility.
abstract: Nck family proteins function as adaptors to couple tyrosine phosphorylation signals to actin cytoskeleton reorganization. Several lines of evidence indicate that Nck family proteins involve in regulating the activity of Rho family GTPases. In the present study, we characterized a novel interaction between Nck-1 with engulfment and cell motility 1 (ELMO1). GST pull-down and co-immunoprecipitation assay demonstrated that the Nck-1-ELMO1 interaction is mediated by the SH2 domain of Nck-1 and the phosphotyrosine residues at position 18, 216, 395, and 511 of ELMO1. A R308K mutant of Nck-1 (in which the SH2 domain was inactive), or a 4YF mutant of ELMO1 lacking these four phosphotyrosine residues, diminished Nck-1-ELMO1 interaction. Conversely, tyrosine phosphatase inhibitor treatment and overexpression of Src family kinase Hck significantly enhanced Nck-1-ELMO1 interaction. Moreover, wild type Nck-1, but not R308K mutant, significantly augmented the interaction between ELMO1 and constitutively active RhoG (RhoG(V12A)), thus promoted Rac1 activation and cell motility. Taken together, the present study characterized a novel Nck-1-ELMO1 interaction and defined a new role for Nck-1 in regulating Rac1 activity.
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China and.
authors.forename: Guo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China and.
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Guangzhou Hospital of Traditional Chinese Medicine, Guangzhou 510515, China.
authors.forename: Fanghua
authors.initials: F
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China and.
authors.forename: Fengxin
authors.initials: F
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China and.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China and. Electronic address: niejing@smu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D019943:Amino Acid Substitution; D002465:Cell Movement / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D020125:Mutation, Missense; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C465214:ELMO1 protein, human; C078332:Nck protein; D015513:Oncogene Proteins; C107953:RAC1 protein, human; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck; D020830:rac1 GTP-Binding Protein
keywords: Adaptor Protein; Cell Motility; Engulfment and Cell Motility 1; Protein Phosphorylation; Protein-Protein Interaction; Ras-related C3 Botulinum Toxin Substrate 1 (Rac1); Tyrosine Phosphorylation