title: Protein kinase A-dependent phosphorylation of Dock180 at serine residue 1250 is important for glioma growth and invasion stimulated by platelet derived-growth factor receptor α.
abstract: BACKGROUND
  Dedicator of cytokinesis 1 (Dock1 or Dock180), a bipartite guanine nucleotide exchange factor for Rac1, plays critical roles in receptor tyrosine kinase-stimulated cancer growth and invasion. Dock180 activity is required in cell migration cancer tumorigenesis promoted by platelet derived growth factor receptor (PDGFR) and epidermal growth factor receptor.
  
  
  METHODS
  To demonstrate whether PDGFRα promotes tumor malignant behavior through protein kinase A (PKA)-dependent serine phosphorylation of Dock180, we performed cell proliferation, viability, migration, immunoprecipitation, immunoblotting, colony formation, and in vivo tumorigenesis assays using established and short-term explant cultures of glioblastoma cell lines.
  
  
  RESULTS
  Stimulation of PDGFRα results in phosphorylation of Dock180 at serine residue 1250 (S1250), whereas PKA inhibitors H-89 and KT5720 oppose this phosphorylation. S1250 locates within the Rac1-binding Dock homology region 2 domain of Dock180, and its phosphorylation activates Rac1, p-Akt, and phosphorylated extracellular signal-regulated kinase 1/2, while promoting cell migration, in vitro. By expressing RNA interference (RNAi)-resistant wild-type Dock180, but not mutant Dock180 S1250L, we were able to rescue PDGFRα-associated signaling and biological activities in cultured glioblastoma multiforme (GBM) cells that had been treated with RNAi for suppression of endogenous Dock180. In addition, expression of the same RNAi-resistant Dock180 rescued an invasive phenotype of GBM cells following intracranial engraftment in immunocompromised mice.
  
  
  CONCLUSIONS
  These data describe an important mechanism by which PDGFRα promotes glioma malignant phenotypes through PKA-dependent serine phosphorylation of Dock180, and the data thereby support targeting the PDGFRα-PKA-Dock180-Rac1 axis for treating GBM with molecular profiles indicating PDGFRα signaling dependency.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Haizhong
authors.initials: H
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Yanli
authors.initials: Y
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Zuoqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Baoshu
authors.initials: B
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Jann N
authors.initials: JN
authors.lastname: Sarkaria
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Raizer
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (H.F., W.Z., Y.H., L.Z., Z.L., W.-Q.G., S.-Y.C.); Department of Neurology, Northwestern Brain Tumor Institute, Center for Genetic Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (H.F., J.J.R., B.H., S.-Y.C.); Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.L.); Department of Neurological Surgery (Y.Y., B.X.); Department of Radiotherapy, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Y.H.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.); Department of Neurological Surgery, Northwestern Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois (C.D.J., A.T.P.).
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D002227:Carbazoles; C099818:DOCK1 protein, human; D007546:Isoquinolines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; C075278:platelet-derived growth factor A; C057416:KT 5720; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017868:Cyclic AMP-Dependent Protein Kinases; D020744:rac GTP-Binding Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: Dock180; PDGFRα; PKA; glioblastomas; phosphorylation