title: CDK11p58 phosphorylation of PAK1 Ser174 promotes DLC2 binding and roles on cell cycle progression.
abstract: CDK11(p58), a CDK11 family Ser/Thr kinase, is a G2/M specific protein and contributed to regulation of cell cycle, transcription and apoptotic signal transduction. Recently, CDK11(p58) has been reported to exert important functions in mitotic process, such as the regulation of bipolar spindle formation and sister chromatid cohesion. Here, we identified p21 activated kinase 1 (PAK1) as a new CDK11(p58) substrate and we mapped a new phosphorylation site of Ser174 on PAK1. By mutagenesis, we created PAK1(174A) and PAK1(174E), which mimic the dephosphorylated and phosphorylated form of PAK1; further analysis showed PAK1(174E) could be recruited to myosin V motor complex through binding to dynein light chain 2 (DLC2). PAK1(174E) could accelerate the mitosis progression in a nocodazole blocked cell model, while PAK1(174A) exhibited an opposite role. Our results indicated PAK1 may serve as a downstream effector of CDK11(p58) during mitosis progression.
authors.affiliation: Gene Research Center, Key Laboratory of Glycoconjugate Research Ministry of Public Health, Shanghai Medical College of Fudan University, Shanghai, P.R. China, 200032.
authors.forename: Xiangfei
authors.initials: X
authors.lastname: Kong
authors.forename: Huachen
authors.initials: H
authors.lastname: Gan
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Hao
authors.forename: Chunming
authors.initials: C
authors.lastname: Cheng
authors.forename: Jianhai
authors.initials: J
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Hong
authors.forename: Junwu
authors.initials: J
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Yayun
authors.initials: Y
authors.lastname: Chi
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yun
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D056743:Cyclin D3; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D056445:Cytoplasmic Dyneins; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D055767:Immobilized Proteins; D047468:Immunoprecipitation; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D024701:Myosin Type V / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D013379:Substrate Specificity; D054462:p21-Activated Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D055767:Immobilized Proteins; D011993:Recombinant Fusion Proteins; D010768:Phosphoserine; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; C427758:DYNLL1 protein, human; D024701:Myosin Type V; D056445:Cytoplasmic Dyneins; C501531:DYNLL2 protein, human; D004398:Dyneins