Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT279WO)

• DTT Name: PAK-2 protein kinase (PAK2)
• Synonyms: p21-activated kinase 2; Serine/threonine-protein kinase PAK 2; S6/H4 kinase; PAK65; PAK-2; Gamma-PAK
• Gene Name: PAK2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Kinase
• UniProt ID: PAK2_HUMAN
• TTD ID: T07766
• EC Number: EC 2.7.11.1
• Sequence:
  MSDNGELEDKPPAPPVRMSSTIFSTGGKDPLSANHSLKPLPSVPEEKKPRHKIISIFSGT
  EKGSKKKEKERPEISPPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKLEQKKNP
  QAVLDVLKFYDSNTVKQKYLSFTPPEKDGFPSGTPALNAKGTEAPAVVTEEEDDDEETAP
  PVIAPRPDHTKSIYTRSVIDPVPAPVGDSHVDGAAKSLDKQKKKTKMTDEEIMEKLRTIV
  SIGDPKKKYTRYEKIGQGASGTVFTATDVALGQEVAIKQINLQKQPKKELIINEILVMKE
  LKNPNIVNFLDSYLVGDELFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLH
  ANQVIHRDIKSDNVLLGMEGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAY
  GPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRDFLNRC
  LEMDVEKRGSAKELLQHPFLKLAKPLSSLTPLIMAAKEAMKSNR
• Function: Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3. 3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation. Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  ErbB signaling pathway (hsa04012)
  Ras signaling pathway (hsa04014)
  Axon guidance (hsa04360)
  Focal adhesion (hsa04510)
  T cell receptor signaling pathway (hsa04660)
  Regulation of actin cytoskeleton (hsa04810)
  Pathogenic Escherichia coli infection (hsa05130)
  Human immunodeficiency virus 1 infection (hsa05170)
  Renal cell carcinoma (hsa05211)
• Reactome Pathway:
  Generation of second messenger molecules (R-HSA-202433)
  Regulation of PAK-2p34 activity by PS-GAP/RHG10 (R-HSA-211728)
  Regulation of activated PAK-2p34 by proteasome mediated degradation (R-HSA-211733)
  Stimulation of the cell death response by PAK-2p34 (R-HSA-211736)
  FCERI mediated MAPK activation (R-HSA-2871796)
  CD28 dependent Vav1 pathway (R-HSA-389359)
  Ephrin signaling (R-HSA-3928664)
  Sema3A PAK dependent Axon repulsion (R-HSA-399954)
  Activation of RAC1 (R-HSA-428540)
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  Smooth Muscle Contraction (R-HSA-445355)
  VEGFR2 mediated vascular permeability (R-HSA-5218920)
  CD209 (DC-SIGN) signaling (R-HSA-5621575)
  RHO GTPases activate PAKs (R-HSA-5627123)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  CDC42 GTPase cycle (R-HSA-9013148)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOH GTPase cycle (R-HSA-9013407)
  RHOG GTPase cycle (R-HSA-9013408)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOU GTPase cycle (R-HSA-9013420)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOV GTPase cycle (R-HSA-9013424)
  Nef and signal transduction (R-HSA-164944)

Molecular Interaction Atlas (MIA) of This DTT

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Il-94	DMPNQ27	Discovery agent	N.A.	Investigative	[1]

References

• [1] PAK1: A Therapeutic Target for Cancer Treatment. ACS Med Chem Lett. 2013 Mar 19;4(5):431-2.