title: PAK1 as a therapeutic target.
abstract: BACKGROUND
  P21-activated kinases (PAKs) are involved in multiple signal transduction pathways in mammalian cells. PAKs, and PAK1 in particular, play a role in such disorders as cancer, mental retardation and allergy. Cell motility, survival and proliferation, the organization and function of cytoskeleton and extracellular matrix, transcription and translation are among the processes affected by PAK1.
  
  
  METHODS
  We discuss the mechanisms that control PAK1 activity, its involvement in physiological and pathophysiological processes, the benefits and the drawbacks of the current tools to regulate PAK1 activity, the evidence that suggests PAK1 as a therapeutic target and the likely directions of future research.
  
  
  RESULTS
  The reader will gain a better knowledge and understanding of the areas described above.
  
  
  CONCLUSIONS
  PAK1 is a promising therapeutic target in cancer and allergen-induced disorders. Its suitability as a target in vascular, neurological and infectious diseases remains ambiguous. Further advancement of this field requires progress on such issues as the development of specific and clinically acceptable inhibitors, the choice between targeting one or multiple PAK isoforms, elucidation of the individual roles of PAK1 targets and the mechanisms that may circumvent inhibition of PAK1.
authors.affiliation: Roswell Park Cancer Institute, Department of Cell Stress Biology, Elm and Carlton Streets, Buffalo, NY 14263, USA.
authors.forename: Julia V
authors.initials: JV
authors.lastname: Kichina
authors.forename: Anna
authors.initials: A
authors.lastname: Goc
authors.forename: Belal
authors.initials: B
authors.lastname: Al-Husein
authors.forename: Payaningal R
authors.initials: PR
authors.lastname: Somanath
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Kandel
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000503:physiopathology; D007109:Immunity / Q000187:drug effects / Q000502:physiology; D008607:Intellectual Disability / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D009928:Organ Specificity; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D007527:Isoenzymes; C515903:PAK1 protein, human; D054462:p21-Activated Kinases