PAK1

PAK1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases PAK1, PAKalpha, p21 (RAC1) activated kinase 1
External IDs MGI: 1339975 HomoloGene: 1936 GeneCards: PAK1
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

5058

18479

Ensembl

ENSG00000149269

ENSMUSG00000030774

UniProt

Q13153

O88643

RefSeq (mRNA)

NM_001128620
NM_002576

NM_011035

RefSeq (protein)

NP_001122092.1
NP_002567.3

n/a

Location (UCSC) Chr 11: 77.32 – 77.47 Mb Chr 7: 97.79 – 97.91 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Serine/threonine-protein kinase PAK 1 is an enzyme that in humans is encoded by the PAK1 gene.[3][4]

PAK1 is one of six members of the PAK family of serine/threonine kinases which are broadly divided into group I (PAK1, PAK2 and PAK3) and group II (PAK4, PAK6 and PAK5/7).[5][6] The PAKs are evolutionary conserved.[7] PAK1 localizes in distinct sub-cellular domains in the cytoplasm and nucleus.[8] PAK1 regulates cytoskeleton remodeling, phenotypic signaling and gene expression, and affects a wide variety of cellular processes such as directional motility, invasion, metastasis, growth, cell cycle progression, angiogenesis.[8][9] PAK1-signaling dependent cellular functions regulate both physiologic and disease processes including, cancer as PAK1 is widely overexpressed and hyperstimulated in human cancer, at-large.[8][10][11]

Discovery

PAK1 was first discovered as an effector of the Rho GTPases in rat brain by Manser and colleagues in 1994.[5] The human PAK1 was identified as a GTP-dependent interacting partner of Rac1 or Cdc42 in the cytosolic fraction from neutrophils, and its complementary DNA was cloned from a human placenta library by Martin and Colleagues in 1995.[6]

Function

PAK proteins are critical effectors that link the Rho_family_of_GTPases (Rho GTPases) to cytoskeleton reorganization and nuclear signaling. PAK proteins, a family of serine/threonine p21-activated kinases, include PAK1, PAK2, PAK3 and PAK4. These proteins serve as targets for the small GTP binding proteins Cdc42 and Rac and have been implicated in a wide range of biological activities. PAK1 regulates cell motility and morphology. Alternative transcripts of this gene have been found, but their full-length natures have not been determined.[12]

Stimulation of PAK1 activity is accompanied by a series of cellular processes that are fundament to the living systems. Being a nodular signaling molecule, PAK1 operates to converging station of a large number of signals triggered by the cell surface proteins as well as upstream activators, and translates into specific phenotypes. At the biochemical level, these activities are regulated by the ability of PAK1 to phosphorylate its effector interacting substrates, which in-turn, set-up a cascades of biochemical events cumulating into a cellular phenotypic response. In addition, PAK1 action is also influenced by its scaffolding activity. Examples of PAK1-regulated cellular processes include, dynamic of actin and microtubule fibers, critical steps during cell cycle progression, motility and invasion, redox and energy metabolism, cell survival, angiogenesis, DNA-repair, hormone sensitivity, and gene expression. Functional implications of the PAK1 signaling are exemplified by its role in oncogenesis,[7] viral pathogenesis,[13][14] cardiovascular dysregulation,[15] and neurological disorders.[16]

Gene and spliced variants

The human PAK1 gene is 153-kb long and consists of 23 exons, six exons for 5’-UTR and 17 exons for protein coding(Gene from review) Alternative splicing of six exons generates 20 transcripts from 308-bp to 3.7-kb long; however, only 12 spliced transcripts are with open reading frames and predicted to code ten proteins and two polypeptides. The remaining 8 transcripts range are for non-coding long RNAs from 308-bp to 863-bp long. In contrast to the human PAK1, murine PAK1 gene generates five transcripts: three protein coding from 508-bp to 3.0-kb long, and two transcripts of about 900-bp for non-coding RNAs.

Protein domains

The core domains of the PAK family include, a kinase domain in the C-terminal region, a p21-binding domain (PBD), and an auto-inhibitory domain (AID) in group I PAKs. Group I PAKs exist in an inactive, closed homodimer conformation wherein AID of one molecule binds to the kinase domain of another molecule, and activated by both GTPase-dependent and -independent manner.[11]

Activation/inhibition

PAK1 contains an autoinhibitory domain that suppresses the catalytic activity of its kinase domain. PAK1 activators relieve this autoinhibition and initiate conformational rearrangements and autoPhosphorylation events leading to kinase activation.

IPA-3 inhibits PAK1. Preactivated PAK1 is resistant to IPA-3. Inhibition in live cells supports a critical role for PAK in PDGF-stimulated ERK activation.[17] Reversible covalent binding of IPA-3 to the PAK1 regulatory domain prevents GTPase docking and the subsequent switch to a catalytically active state.[18]

PAK1 knockdown in prostate cancer cells is associated with reduced motility, reduced MMP9 secretion and increased TGFβ expression, which in these cases, is growth inhibitory. However, IPA-3's pharmacokinetic properties as well as undesirable redox effects in cells, due to the continuous reduction of the sulfhydryl moiety, make it unsuitable for clinical development.[18]

Upstream activators

PAK1 activity is stimulated by a large number of upstream activators and signals, ranging from EGF,[19] heregulin-beta 1,[20] VEGF,[21] basic fibroblast growth factor,[22] platelet-derived growth factor,[23] estrogen,[24] lysophosphatidic acid,[25] phosphoinositides,[26] ETK,[27] AKT,[28] JAK2,[29] ERK,[30] casein kinase II,[31] Rac3,[32] chemokine (C-X-C motif) ligand 1,[33] breast cancer anti-estrogen resistance 3,[34] Kaposi's sarcoma-associated herpesvirus-G protein-coupled receptor,[35] ARG-binding protein 2γ,[36] hepatitis B virus X protein,[37] STE20-related kinase adaptor protein α,[38] RhoI,[39] Klotho,[40] N-acetylglucosaminyl transferase V,[41] B-Raf proto-oncogene,[42] casein kinase 2-interacting protein 1,[43] and filamin A.[44]

Downstream effector targets

Functions of PAK1 are regulated by its ability to phosphorylate downstream effector substrates, scaffold activity, redistribution to distinct sub-cellular cellular sub-domains, stimulation or repression of expression of its genomic targets either directly or indirectly, or by all of these mechanisms. Representative PAK1 effector substrates in cancer cells include: Stathmin-S16,[45] Merlin-S518,[46] Vimentin-S25-S38-S50-S65-S72,[47] Histone H3-S10,[48] FilaminA-S2152,[44] Estrogen receptor-alpha-S305,[49] signal transducer and activator of transcription 5a-S779,[50] C-terminal binding protein 1-S158,[51] Raf1-S338,[52] Arpc1b-T21,[53] DLC1-S88,[54] phosphoglucomutase 1-T466,[55] SMART/HDAC1-associated repressor protein-S3486-T3568,[56] Tubulin Cofactor B-S65-S128,[57] Snail-S246 [58] vascular endothelial-cadherin-S665,[59] poly(RC) binding protein 1-T60-S246,[60] integrin-linked kinase 1-T173-S246,[61] epithelium-specific Ets transcription factor 1-S207,[62] ErbB3 binding protein 1-T261,[63] nuclear receptor-interacting factor 3-S28,[64] SRC3-delta4-T56-S659-676,[65] beta-catenin-S675,[66] BAD-S111,[67] BAD-S112,S136,[68] MEK1-S298,[69][70] CRKII-S41,[71] MORC family CW-type zinc finger 2-S739,[72][73] Paxillin-S258,[13] and Paxillin-S273.[74]

Genomic targets

PAK1 and/or PAK1-dependent signals modulate the expression of its genomic targets,[7] including, vascular endothelial growth factor,[21] Cyclin D1,[75] phosphofructokinase-muscle isoform,[76] nuclear factor of activated T-cell,[76] Cyclin B1,[77] Tissue Factor and tissue factor pathway inhibitor,[78] Metalloproteinase 9,[79] and fibronectin.[80]

Inhibitors

The levels of PAK1 activity under various experimental and physiological conditions are inhibited by PP1,[81] hPIP1,[82] NESH,[83] Merlin,[84] CRIPak,[85] LKB1,[86] Mesalamine,[87] Glaucarubinone,[88] Myricetin,[89] β-elemene,[90] miR-7,[91] miR-let-7,[92] miR-145.[93] In addition, various anti-PAK small molecules such as FRAX1036,[94][95] OSU-03012,[96] and IPA-3[97] are currently being developed by academia and pharmaceutical industry.[98][99][100]

Interactions

PAK1 has been shown to interact with:

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J (May 1996). "Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway". Current Biology. 6 (5): 598–605. doi:10.1016/S0960-9822(02)00546-8. PMID 8805275.
  4. ↑ Bekri S, Adélaïde J, Merscher S, Grosgeorge J, Caroli-Bosc F, Perucca-Lostanlen D, Kelley PM, Pébusque MJ, Theillet C, Birnbaum D, Gaudray P (Apr 1998). "Detailed map of a region commonly amplified at 11q13-->q14 in human breast carcinoma". Cytogenetics and Cell Genetics. 79 (1-2): 125–31. doi:10.1159/000134699. PMID 9533029.
  5. 1 2 Manser E, Leung T, Salihuddin H, Zhao ZS, Lim L (January 1994). "A brain serine/threonine protein kinase activated by Cdc42 and Rac1". Nature. 367 (6458): 40–6. doi:10.1038/367040a0. PMID 8107774.
  6. 1 2 Martin GA, Bollag G, McCormick F, Abo A (May 1995). "A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20". The EMBO Journal. 14 (9): 1970–8. PMID 7744004.
  7. 1 2 3 Kumar A, Molli PR, Pakala SB, Bui Nguyen TM, Rayala SK, Kumar R (July 2009). "PAK thread from amoeba to mammals". Journal of Cellular Biochemistry. 107 (4): 579–85. doi:10.1002/jcb.22159. PMID 19350548.
  8. 1 2 3 Vadlamudi RK, Kumar R (December 2003). "P21-activated kinases in human cancer". Cancer Metastasis Reviews. 22 (4): 385–93. PMID 12884913.
  9. ↑ Kumar R, Gururaj AE, Barnes CJ (June 2006). "p21-activated kinases in cancer". Nature Reviews. Cancer. 6 (6): 459–71. doi:10.1038/nrc1892. PMID 16723992.
  10. ↑ Radu M, Semenova G, Kosoff R, Chernoff J (January 2014). "PAK signalling during the development and progression of cancer". Nature Reviews. Cancer. 14 (1): 13–25. PMID 24505617.
  11. 1 2 Kumar R, Li DQ (2016). "PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future Oncobiology". Advances in Cancer Research. 130: 137–209. doi:10.1016/bs.acr.2016.01.002. PMID 27037753.
  12. ↑ "Entrez Gene: PAK1 p21/Cdc42/Rac1-activated kinase 1 (STE20 homolog, yeast)".
  13. 1 2 Lee JH, Wittki S, Bräu T, Dreyer FS, Krätzel K, Dindorf J, Johnston IC, Gross S, Kremmer E, Zeidler R, Schlötzer-Schrehardt U, Lichtenheld M, Saksela K, Harrer T, Schuler G, Federico M, Baur AS (February 2013). "HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases". Molecular Cell. 49 (4): 668–79. doi:10.1016/j.molcel.2012.12.004. PMID 23317503.
  14. ↑ Van den Broeke C, Radu M, Chernoff J, Favoreel HW (March 2010). "An emerging role for p21-activated kinases (Paks) in viral infections". Trends in Cell Biology. 20 (3): 160–9. doi:10.1016/j.tcb.2009.12.005. PMID 20071173.
  15. ↑ Ke Y, Wang X, Jin XY, Solaro RJ, Lei M (December 2014). "PAK1 is a novel cardiac protective signaling molecule". Frontiers of Medicine. 8 (4): 399–403. doi:10.1007/s11684-014-0380-9. PMID 25416031.
  16. ↑ Ma QL, Yang F, Frautschy SA, Cole GM (April 2012). "PAK in Alzheimer disease, Huntington disease and X-linked mental retardation". Cellular Logistics. 2 (2): 117–125. doi:10.4161/cl.21602. PMID 23162743.
  17. ↑ Deacon SW, Beeser A, Fukui JA, Rennefahrt UE, Myers C, Chernoff J, Peterson JR (April 2008). "An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase". Chemistry & Biology. 15 (4): 322–31. doi:10.1016/j.chembiol.2008.03.005. PMC 4353635Freely accessible. PMID 18420139.
  18. 1 2 Goc A, Al-Azayzih A, Abdalla M, Al-Husein B, Kavuri S, Lee J, Moses K, Somanath PR (February 2013). "P21 activated kinase-1 (Pak1) promotes prostate tumor growth and microinvasion via inhibition of transforming growth factor β expression and enhanced matrix metalloproteinase 9 secretion". The Journal of Biological Chemistry. 288 (5): 3025–35. doi:10.1074/jbc.M112.424770. PMC 3561527Freely accessible. PMID 23258534.
  19. ↑ Galisteo ML, Chernoff J, Su YC, Skolnik EY, Schlessinger J (August 1996). "The adaptor protein Nck links receptor tyrosine kinases with the serine-threonine kinase Pak1". The Journal of Biological Chemistry. 271 (35): 20997–1000. PMID 8798379.
  20. ↑ Adam L, Vadlamudi R, Kondapaka SB, Chernoff J, Mendelsohn J, Kumar R (October 1998). "Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase". The Journal of Biological Chemistry. 273 (43): 28238–46. PMID 9774445.
  21. 1 2 Bagheri-Yarmand R, Vadlamudi RK, Wang RA, Mendelsohn J, Kumar R (December 2000). "Vascular endothelial growth factor up-regulation via p21-activated kinase-1 signaling regulates heregulin-beta1-mediated angiogenesis". The Journal of Biological Chemistry. 275 (50): 39451–7. doi:10.1074/jbc.M006150200. PMID 10967114.
  22. ↑ Shin KS, Shin EY, Lee CS, Quan SH, Woo KN, Soung NK, Kwak SJ, Kim SR, Kim EG (May 2002). "Basic fibroblast growth factor-induced translocation of p21-activated kinase to the membrane is independent of phospholipase C-gamma1 in the differentiation of PC12 cells". Experimental & Molecular Medicine. 34 (2): 172–6. doi:10.1038/emm.2002.25. PMID 12085993.
  23. ↑ He H, Levitzki A, Zhu HJ, Walker F, Burgess A, Maruta H (July 2001). "Platelet-derived growth factor requires epidermal growth factor receptor to activate p21-activated kinase family kinases". The Journal of Biological Chemistry. 276 (29): 26741–4. doi:10.1074/jbc.C100229200. PMID 11356824.
  24. ↑ Mazumdar A, Kumar R (January 2003). "Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells". FEBS Letters. 535 (1-3): 6–10. PMID 12560069.
  25. ↑ Jung ID, Lee J, Lee KB, Park CG, Kim YK, Seo DW, Park D, Lee HW, Han JW, Lee HY (April 2004). "Activation of p21-activated kinase 1 is required for lysophosphatidic acid-induced focal adhesion kinase phosphorylation and cell motility in human melanoma A2058 cells". European Journal of Biochemistry. 271 (8): 1557–65. doi:10.1111/j.1432-1033.2004.04066.x. PMID 15066181.
  26. ↑ Strochlic TI, Viaud J, Rennefahrt UE, Anastassiadis T, Peterson JR (November 2010). "Phosphoinositides are essential coactivators for p21-activated kinase 1". Molecular Cell. 40 (3): 493–500. doi:10.1016/j.molcel.2010.10.015. PMID 21070974.
  27. ↑ Bagheri-Yarmand R, Mandal M, Taludker AH, Wang RA, Vadlamudi RK, Kung HJ, Kumar R (August 2001). "Etk/Bmx tyrosine kinase activates Pak1 and regulates tumorigenicity of breast cancer cells". The Journal of Biological Chemistry. 276 (31): 29403–9. doi:10.1074/jbc.M103129200. PMID 11382770.
  28. ↑ Zhou GL, Zhuo Y, King CC, Fryer BH, Bokoch GM, Field J (November 2003). "Akt phosphorylation of serine 21 on Pak1 modulates Nck binding and cell migration". Molecular and Cellular Biology. 23 (22): 8058–69. PMID 14585966.
  29. ↑ Rider L, Shatrova A, Feener EP, Webb L, Diakonova M (October 2007). "JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions". The Journal of Biological Chemistry. 282 (42): 30985–96. doi:10.1074/jbc.M701794200. PMID 17726028.
  30. ↑ Yuan L, Santi M, Rushing EJ, Cornelison R, MacDonald TJ (October 2010). "ERK activation of p21 activated kinase-1 (Pak1) is critical for medulloblastoma cell migration". Clinical & Experimental Metastasis. 27 (7): 481–91. doi:10.1007/s10585-010-9337-9. PMID 20526801.
  31. ↑ Shin YJ, Kim YB, Kim JH (September 2013). "Protein kinase CK2 phosphorylates and activates p21-activated kinase 1". Molecular Biology of the Cell. 24 (18): 2990–9. doi:10.1091/mbc.E13-04-0204. PMID 23885116.
  32. ↑ Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG (January 2000). "Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 185–9. PMID 10618392.
  33. ↑ Wang D, Sai J, Richmond A (February 2003). "Cell surface heparan sulfate participates in CXCL1-induced signaling". Biochemistry. 42 (4): 1071–7. doi:10.1021/bi026425a. PMID 12549928.
  34. ↑ Cai D, Iyer A, Felekkis KN, Near RI, Luo Z, Chernoff J, Albanese C, Pestell RG, Lerner A (October 2003). "AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter". Cancer Research. 63 (20): 6802–8. PMID 14583477.
  35. ↑ Dadke D, Fryer BH, Golemis EA, Field J (December 2003). "Activation of p21-activated kinase 1-nuclear factor kappaB signaling by Kaposi's sarcoma-associated herpes virus G protein-coupled receptor during cellular transformation". Cancer Research. 63 (24): 8837–47. PMID 14695200.
  36. ↑ Yuan ZQ, Kim D, Kaneko S, Sussman M, Bokoch GM, Kruh GD, Nicosia SV, Testa JR, Cheng JQ (June 2005). "ArgBP2gamma interacts with Akt and p21-activated kinase-1 and promotes cell survival". The Journal of Biological Chemistry. 280 (22): 21483–90. doi:10.1074/jbc.M500097200. PMID 15784622.
  37. ↑ Xu J, Liu H, Chen L, Wang S, Zhou L, Yun X, Sun L, Wen Y, Gu J (July 2012). "Hepatitis B virus X protein confers resistance of hepatoma cells to anoikis by up-regulating and activating p21-activated kinase 1". Gastroenterology. 143 (1): 199–212.e4. doi:10.1053/j.gastro.2012.03.053. PMID 22484303.
  38. ↑ Eggers CM, Kline ER, Zhong D, Zhou W, Marcus AI (May 2012). "STE20-related kinase adaptor protein α (STRADα) regulates cell polarity and invasion through PAK1 signaling in LKB1-null cells". The Journal of Biological Chemistry. 287 (22): 18758–68. doi:10.1074/jbc.M111.316422. PMID 22493453.
  39. ↑ Ho H, Aruri J, Kapadia R, Mehr H, White MA, Ganesan AK (November 2012). "RhoJ regulates melanoma chemoresistance by suppressing pathways that sense DNA damage". Cancer Research. 72 (21): 5516–28. doi:10.1158/0008-5472.CAN-12-0775. PMID 22971344.
  40. ↑ Chen L, Liu H, Liu J, Zhu Y, Xu L, He H, Zhang H, Wang S, Wu Q, Liu W, Liu Y, Pan D, Ren S, Xu J, Gu J (2013). "Klotho endows hepatoma cells with resistance to anoikis via VEGFR2/PAK1 activation in hepatocellular carcinoma". PloS One. 8 (3): e58413. doi:10.1371/journal.pone.0058413. PMID 23516476.
  41. ↑ Liu J, Liu H, Zhang W, Wu Q, Liu W, Liu Y, Pan D, Xu J, Gu J (September 2013). "N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation". Glycobiology. 23 (9): 1097–109. doi:10.1093/glycob/cwt049. PMID 23811795.
  42. ↑ McCarty SK, Saji M, Zhang X, Knippler CM, Kirschner LS, Fernandez S, Ringel MD (2014). "BRAF activates and physically interacts with PAK to regulate cell motility". Endocrine-Related Cancer. 21 (6): 865–77. doi:10.1530/ERC-14-0424. PMID 25228413.
  43. ↑ Kim YB, Shin YJ, Roy A, Kim JH (August 2015). "The Role of the Pleckstrin Homology Domain-containing Protein CKIP-1 in Activation of p21-activated Kinase 1 (PAK1)". The Journal of Biological Chemistry. 290 (34): 21076–85. doi:10.1074/jbc.M115.675124. PMID 26160174.
  44. 1 2 Vadlamudi RK, Li F, Adam L, Nguyen D, Ohta Y, Stossel TP, Kumar R (September 2002). "Filamin is essential in actin cytoskeletal assembly mediated by p21-activated kinase 1". Nature Cell Biology. 4 (9): 681–90. doi:10.1038/ncb838. PMID 12198493.
  45. ↑ Daub H, Gevaert K, Vandekerckhove J, Sobel A, Hall A (January 2001). "Rac/Cdc42 and p65PAK regulate the microtubule-destabilizing protein stathmin through phosphorylation at serine 16". The Journal of Biological Chemistry. 276 (3): 1677–80. doi:10.1074/jbc.C000635200. PMID 11058583.
  46. ↑ Xiao GH, Beeser A, Chernoff J, Testa JR (January 2002). "p21-activated kinase links Rac/Cdc42 signaling to merlin". The Journal of Biological Chemistry. 277 (2): 883–6. doi:10.1074/jbc.C100553200. PMID 11719502.
  47. ↑ Goto H, Tanabe K, Manser E, Lim L, Yasui Y, Inagaki M (February 2002). "Phosphorylation and reorganization of vimentin by p21-activated kinase (PAK)". Genes to Cells. 7 (2): 91–7. PMID 11895474.
  48. ↑ Li F, Adam L, Vadlamudi RK, Zhou H, Sen S, Chernoff J, Mandal M, Kumar R (August 2002). "p21-activated kinase 1 interacts with and phosphorylates histone H3 in breast cancer cells". EMBO Reports. 3 (8): 767–73. doi:10.1093/embo-reports/kvf157. PMID 12151336.
  49. ↑ Wang RA, Mazumdar A, Vadlamudi RK, Kumar R (October 2002). "P21-activated kinase-1 phosphorylates and transactivates estrogen receptor-alpha and promotes hyperplasia in mammary epithelium". The EMBO Journal. 21 (20): 5437–47. PMID 12374744.
  50. ↑ Wang RA, Vadlamudi RK, Bagheri-Yarmand R, Beuvink I, Hynes NE, Kumar R (May 2003). "Essential functions of p21-activated kinase 1 in morphogenesis and differentiation of mammary glands". The Journal of Cell Biology. 161 (3): 583–92. doi:10.1083/jcb.200212066. PMID 12732616.
  51. ↑ Barnes CJ, Vadlamudi RK, Mishra SK, Jacobson RH, Li F, Kumar R (August 2003). "Functional inactivation of a transcriptional corepressor by a signaling kinase". Nature Structural Biology. 10 (8): 622–8. doi:10.1038/nsb957. PMID 12872159.
  52. ↑ Gurdon JB (January 1992). "The generation of diversity and pattern in animal development". Cell. 68 (2): 185–99. PMID 1733498.
  53. ↑ Vadlamudi RK, Li F, Barnes CJ, Bagheri-Yarmand R, Kumar R (February 2004). "p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate". EMBO Reports. 5 (2): 154–60. doi:10.1038/sj.embor.7400079. PMID 14749719.
  54. ↑ Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R (June 2004). "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes". Cancer Cell. 5 (6): 575–85. doi:10.1016/j.ccr.2004.05.022. PMID 15193260.
  55. ↑ Gururaj A, Barnes CJ, Vadlamudi RK, Kumar R (October 2004). "Regulation of phosphoglucomutase 1 phosphorylation and activity by a signaling kinase". Oncogene. 23 (49): 8118–27. doi:10.1038/sj.onc.1207969. PMID 15378030.
  56. ↑ Vadlamudi RK, Manavathi B, Singh RR, Nguyen D, Li F, Kumar R (June 2005). "An essential role of Pak1 phosphorylation of SHARP in Notch signaling". Oncogene. 24 (28): 4591–6. doi:10.1038/sj.onc.1208672. PMID 15824732.
  57. ↑ Vadlamudi RK, Barnes CJ, Rayala S, Li F, Balasenthil S, Marcus S, Goodson HV, Sahin AA, Kumar R (May 2005). "p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B". Molecular and Cellular Biology. 25 (9): 3726–36. doi:10.1128/MCB.25.9.3726-3736.2005. PMID 15831477.
  58. ↑ Yang Z, Rayala S, Nguyen D, Vadlamudi RK, Chen S, Kumar R (April 2005). "Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions". Cancer Research. 65 (8): 3179–84. doi:10.1158/0008-5472.CAN-04-3480. PMID 15833848.
  59. ↑ Gavard J, Gutkind JS (November 2006). "VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin". Nature Cell Biology. 8 (11): 1223–34. doi:10.1038/ncb1486. PMID 17060906.
  60. ↑ Meng Q, Rayala SK, Gururaj AE, Talukder AH, O'Malley BW, Kumar R (April 2007). "Signaling-dependent and coordinated regulation of transcription, splicing, and translation resides in a single coregulator, PCBP1". Proceedings of the National Academy of Sciences of the United States of America. 104 (14): 5866–71. doi:10.1073/pnas.0701065104. PMID 17389360.
  61. ↑ Acconcia F, Barnes CJ, Singh RR, Talukder AH, Kumar R (April 2007). "Phosphorylation-dependent regulation of nuclear localization and functions of integrin-linked kinase". Proceedings of the National Academy of Sciences of the United States of America. 104 (16): 6782–7. doi:10.1073/pnas.0701999104. PMID 17420447.
  62. ↑ Manavathi B, Rayala SK, Kumar R (July 2007). "Phosphorylation-dependent regulation of stability and transforming potential of ETS transcriptional factor ESE-1 by p21-activated kinase 1". The Journal of Biological Chemistry. 282 (27): 19820–30. doi:10.1074/jbc.M702309200. PMID 17491012.
  63. ↑ Akinmade D, Talukder AH, Zhang Y, Luo WM, Kumar R, Hamburger AW (March 2008). "Phosphorylation of the ErbB3 binding protein Ebp1 by p21-activated kinase 1 in breast cancer cells". British Journal of Cancer. 98 (6): 1132–40. doi:10.1038/sj.bjc.6604261. PMID 18283314.
  64. ↑ Talukder AH, Li DQ, Manavathi B, Kumar R (September 2008). "Serine 28 phosphorylation of NRIF3 confers its co-activator function for estrogen receptor-alpha transactivation". Oncogene. 27 (39): 5233–42. doi:10.1038/onc.2008.151. PMID 18521086.
  65. ↑ Long W, Yi P, Amazit L, LaMarca HL, Ashcroft F, Kumar R, Mancini MA, Tsai SY, Tsai MJ, O'Malley BW (February 2010). "SRC-3Delta4 mediates the interaction of EGFR with FAK to promote cell migration". Molecular Cell. 37 (3): 321–32. doi:10.1016/j.molcel.2010.01.004. PMID 20159552.
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