Pak Family

Aliases: p21/Cdc42/Rac1-activated kinase 1 (yeast Ste20-related), p21-activated kinase 1, STE20 homolog, yeast, p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast), PAKalpha, PAK1, MGC130000, MGC130001

Pfam Domain Structure

From PAK1 (human) - phosphorylation sites added via direct mapping

Members of the Pak Family
1: PAK1 » Human Mouse Rat Chicken Fly Worm
CMKB PAK1 Pak1 Pak1 PAK1 Pak pak-1
Entrez Gene 5058 18479 29431 419083 44039 180873
Uniprot PAK1_HUMAN PAK1_MOUSE PAK1_RAT - - PAK1_CAEEL
OMIM 602590 - - - - -
Reagents - - - - - -
Results 2 available 1 available - - 2 available -
2: PAK2 » Human Mouse Rat Chicken Fly Worm
CMKB PAK2 Pak2 Pak2 PAK2 - -
Entrez Gene 5062 224105 29432 424860 - -
Uniprot PAK2_HUMAN PAK2_MOUSE PAK2_RAT - - -
OMIM 605022 - - - - -
Reagents - - - - - -
Results 3 available - - - - -
3: PAK3 » Human Mouse Rat Chicken Fly Worm
CMKB PAK3 Pak3 Pak3 PAK3 - -
Entrez Gene 5063 18481 29433 422342 - -
Uniprot PAK3_HUMAN PAK3_MOUSE PAK3_RAT - - -
OMIM 300142 - - - - -
Reagents - - - - - -
Results 2 available - - - - -
4: PAK4 » Human Mouse Rat Chicken Fly Worm
CMKB PAK4 Pak4 Pak4 - - -
Entrez Gene 10298 70584 292756 - - -
Uniprot PAK4_HUMAN PAK4_MOUSE - - - -
OMIM 605451 - - - - -
Reagents - - - - - -
Results 5 available - - - - -
5: PAK6 » Human Mouse Rat Chicken Fly Worm
CMKB PAK6 Pak6 Pak6 PAK6 - pak-2
Entrez Gene 56924 214230 296078 428837 - 179527
Uniprot PAK6_HUMAN PAK6_MOUSE - - - -
OMIM 608110 - - - - -
Reagents - - - - - -
Results 2 available - - - - -
6: PAK7 » Human Mouse Rat Chicken Fly Worm
CMKB PAK7 Pak7 Pak7 - mbt -
Entrez Gene 57144 241656 311450 - 32631 -
Uniprot PAK7_HUMAN PAK7_MOUSE - - PAKM_DROME -
OMIM 608038 - - - - -
Reagents - - - - - -
Results 2 available - - - 1 available -
Family Summary

PAK (p21-activated kinase) is a serine/threonine kinase that binds to and is activated by Rho family GTPases. The PAK family of kinases is highly conserved among species. PAK family members have an N-terminal kinase domain and a C-terminal p21 Rac and Cdc-42-binding domain. The binding of Rho family GTPases to the C-terminus of PAK causes a conformational change resulting in autophosphorylation and activation of the kinase. PAK family members have been shown to play a role in actin polymerization and cytoskeletal dynamics. The association between NCK and PAK1 has been shown to occur through the first N-terminal polyproline domain of PAK1 and an SH3 domain of NCK. SLP-76 has been shown to provide a scaffold for the assembly of NCK/PAK1 in close proximity with VAV and RAC leading to activation of PAK1 and subsequent downstream cytoskeletal events.

References
  1. Bokoch GM. Biology of the p21-activated kinases. Annu. Rev. Biochem. 2003; 72:743-81 (PubMed)
  2. Chew TL, Masaracchia RA, Goeckeler ZM, Wysolmerski RB. Phosphorylation of non-muscle myosin II regulatory light chain by p21-activated kinase (gamma-PAK). J. Muscle Res. Cell. Motil. 1998; 19:839-54 (PubMed)
  3. Cotteret S, Chernoff J. Pak GITs to Aurora-A. Dev. Cell 2005; 9:573-4 (PubMed)
  4. Dummler B, Ohshiro K, Kumar R, Field J. Pak protein kinases and their role in cancer. Cancer Metastasis Rev. 2009; 28:51-63 (PubMed)
  5. Fryer BH, Field J. Rho, Rac, Pak and angiogenesis: old roles and newly identified responsibilities in endothelial cells. Cancer Lett. 2005; 229:13-23 (PubMed)
  6. Gerthoffer WT. Actin cytoskeletal dynamics in smooth muscle contraction. Can. J. Physiol. Pharmacol. 2005; 83:851-6 (PubMed)
  7. Hoefen RJ, Berk BC. The multifunctional GIT family of proteins. J. Cell. Sci. 2006; 119:1469-75 (PubMed)
  8. Hofmann C, Shepelev M, Chernoff J. The genetics of Pak. J. Cell. Sci. 2004; 117:4343-54 (PubMed)
  9. Howe AK. Regulation of actin-based cell migration by cAMP/PKA. Biochim. Biophys. Acta 2004; 1692:159-74 (PubMed)
  10. Juliano RL, Reddig P, Alahari S, Edin M, Howe A, Aplin A. Integrin regulation of cell signalling and motility. Biochem. Soc. Trans. 2004; 32:443-6 (PubMed)
  11. Labruyère E, Guillén N. Host tissue invasion by Entamoeba histolytica is powered by motility and phagocytosis. Arch. Med. Res. 2006; 37:253-8 (PubMed)
  12. Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 1994; 367:40-6 (PubMed)
  13. Parrini MC, Matsuda M, de Gunzburg J. Spatiotemporal regulation of the Pak1 kinase. Biochem. Soc. Trans. 2005; 33:646-8 (PubMed)
  14. Settleman J. PAK-in' up cGMP for the move. Cell 2007; 128:237-8 (PubMed)
  15. Vlahou G, Rivero F. Rho GTPase signaling in Dictyostelium discoideum: insights from the genome. Eur. J. Cell Biol. 2006; 85:947-59 (PubMed)
  16. Zhao ZS, Manser E. PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation. Biochem. J. 2005; 386:201-14 (Full Text)
Consortium Results & Data
Results & Data
Ortholog Species Type Description Method Status Source Publications
PAK1 none binding partner Pak1 Ectopic expression in HEK cells 13 proteins exclusively co-purified with Pak1 Horwitz Mayhew et al.
PAK1 none phosphorylation site Pak1 Ectopic expression in HEK cells 30 phospho-sites in 80.5% coverage of 529 aa Horwitz Mayhew et al.
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK1
Aliases: PAKalpha
Entrez Gene: 5058
siRNA catalog
p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)
mRNA: NM_002576
Library: Kinase
Classification: Tyr Kinase
Focal Adhesion Related: Yes
Final bin: Discordant
SMARTpool bin: Low Alamar
Avg area: 2.14
Avg Alamar: 0.79
Knockdown %: 90-100
ERBB2: Impaired
BCL2: Low Alamar
PAK1
Link
PAK1
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK1
Aliases: PAKalpha
Entrez Gene: 5058
siRNA catalog
p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)
mRNA: NM_002576
Library: Kinase
PAK1
Link
PAK1
Link
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK7
Aliases: PAK5
Entrez Gene: 57144
siRNA catalog
p21(CDKN1A)-activated kinase 7
mRNA: NM_020341
Library: Kinase
Classification: Atypical Kinase
Final bin: No Phenotype
SMARTpool bin: No change
Avg area: 1.87
Avg Alamar: 0.90
Knockdown %: failed
  PAK7
Link
PAK7
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK7
Aliases: PAK5
Entrez Gene: 57144
siRNA catalog
p21(CDKN1A)-activated kinase 7
mRNA: NM_020341
Library: Kinase
PAK7
Link
PAK7
Link
Discovery» PyMT invasive data
Gene mRNA Description Expression Ratio
Pak1
Entrez Gene: 18479
mRNA: AA061378
UniGene: Mm.260227
P21 (CDKN1A)-activated kinase 1 2.01
Discovery» Drosophila Morphology Genes
Gene Name Cell Count/
Normalization
Stellate11
NumCorners
Stellate22
Binsum6
Non-Spreading3
CG18582
Entrez Gene: 32631
mushroom bodies tiny
Aliases: anon-fast-evolving-1G7
11.063
0.850
0.931 0.952 Actin: 1.024
Area: 1.182
Ratio: 0.866
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK4
Entrez Gene: 10298
siRNA catalog
p21(CDKN1A)-activated kinase 4
mRNA: NM_005884
Library: Kinase
Classification: Atypical Kinase
Final bin: No Phenotype
SMARTpool bin: No change
Avg area: 1.63
Avg Alamar: 1.05
Knockdown %: 80-90
  PAK4
Link
PAK4
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK4
Entrez Gene: 10298
siRNA catalog
p21(CDKN1A)-activated kinase 4
mRNA: NM_005884
Library: Kinase
PAK4
Link
PAK4
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00014068 PAK4 SPLICE ISOFORM 1 OF SERINE/THREONINE-PROTEIN KINASE PAK 4. 3 3 7 3 2.33
Proteomics» Table 2. Proteins in major organelles and subcellular compartments
IPI Locus Description CB Spectra PD Spectra ratio Location
IPI00014068 PAK4 SPLICE ISOFORM 1 OF SERINE/THREONINE-PROTEIN KINASE PAK 4. 3 7 2.33 Golgi
Proteomics» Table 3. Quantitation of phosphopeptides identified in Pseudopodium (PD) and Cell Body (CB) fractions
IPI Locus Description peptide pdcb_p pdcb_t ratio Mouse homology Rat homology Zebrafish homology sd Variable sites
IPI00014068 PAK4 SERINE/THREONINE-PROTEIN KINASE PAK 4. S*LVGTPYWMAPELISR 0.7 2.33 0.3 +++ +++ +++ 0.08  
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK6
Aliases: PAK5
Entrez Gene: 56924
siRNA catalog
p21(CDKN1A)-activated kinase 6
mRNA: NM_020168
Library: Kinase
Classification: Ser/Thr Kinase
Final bin: Discordant
SMARTpool bin: No change
Avg area: 0.91
Avg Alamar: 1.02
Knockdown %: <20
  PAK6
Link
PAK6
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK6
Aliases: PAK5
Entrez Gene: 56924
siRNA catalog
p21(CDKN1A)-activated kinase 6
mRNA: NM_020168
Library: Kinase
PAK6
Link
PAK6
Link
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK3
Aliases: bPAK, MRX30, MRX47, OPHN3, hPAK3, CDKN1A, PAK3beta
Entrez Gene: 5063
siRNA catalog
p21 (CDKN1A)-activated kinase 3
mRNA: NM_002578
Library: Kinase
Classification: Ser/Thr Kinase
Final bin: No Phenotype
SMARTpool bin: No change
Avg area: 1.62
Avg Alamar: 0.95
Knockdown %: failed
  PAK3
Link
PAK3
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK3
Aliases: bPAK, MRX30, MRX47, OPHN3, hPAK3, CDKN1A, PAK3beta
Entrez Gene: 5063
siRNA catalog
p21 (CDKN1A)-activated kinase 3
mRNA: NM_002578
Library: Kinase
PAK3
Link
PAK3
Link
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
PAK2
Aliases: PAK65, PAKgamma
Entrez Gene: 5062
siRNA catalog
p21 (CDKN1A)-activated kinase 2
mRNA: NM_002577
Library: Kinase
Classification: Tyr Kinase
Final bin: No Phenotype
SMARTpool bin: No change
Avg area: 1.81
Avg Alamar: 0.85
Knockdown %: 80-90
  PAK2
Link
PAK2
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
PAK2
Aliases: PAK65, PAKgamma
Entrez Gene: 5062
siRNA catalog
p21 (CDKN1A)-activated kinase 2
mRNA: NM_002577
Library: Kinase
PAK2
Link
PAK2
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00419979 PAK2 PAK2 PROTEIN. 28 12 56 18 2.00
Discovery» Drosophila Migration Genes
Gene Name Function Cell
Type
Phenotypes Reagents/
Alleles
Reference
Pak
Entrez: CG10295
Flybase: FBgn0014001
PAK-kinase protein serine/threonine kinase activity dorsal closure Loss of function: dorsal closure defects
Autonomous: Both amnioserosa and epidermis
Pak20, PakAID (autoinhibitory domain of dPak) Conder, 2004
Discovery» Drosophila Morphology Genes
Gene Name Cell Count/
Normalization
Stellate11
NumCorners
Stellate22
Binsum6
Non-Spreading3
CG10295
Entrez Gene: 44039
PAK-kinase
Aliases: Pak1 kinase; p21-associated kinase; p-21 activated kinase; p21-activated kinase; Pak kinase; PAK kinase; p21-activated serine/threonine kinase
10.125
1.138
0.99 0.989 Actin: 0.871
Area: 0.948
Ratio: 0.919
Consortium Related Products*
Biosensors » activity page
Ortholog Species Name Type Source Publications
PAK1 none PAK Generically encoded caged PAK inhibitor Hahn
-

* The resources presented here are largely those generated by the Consortium. The sidebar provides public databases that complement Consortium activities. For mice and biosensors, a public database is not available and therefore we have attempted to generate a migration related list for your convenience.

The primary classification of CMKB families is the homeomorphic family, whose members are both homologous (evolved from a common ancestor) and homeomorphic (sharing full-length sequence similarity and a common domain architecture).