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Recombinant Human Serine/threonine-protein kinase PAK 4 (PAK4)

  • 中文名稱:
    人PAK4重組蛋白
  • 貨號:
    CSB-EP017408HU
  • 規格:
    ¥1344
  • 圖片:
    • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • 其他:

產品詳情

  • 純度:
    Greater than 90% as determined by SDS-PAGE.
  • 基因名:
  • Uniprot No.:
  • 別名:
    KIAA1142; p21 activated kinase 4; p21 Cdc42/Rac1-actiated kinase 4; P21 protein (Cdc42/Rac) activated kinase 4; p21(CDKN1A) activated kinase 4; p21-activated kinase 4; PAK 4; PAK-4; Pak4; PAK4_HUMAN; Protein kinase related to S.cerevisiae STE20 effector for Cdc42Hs; Serine threonine kinase PAK 4; Serine/threonine protein kinase PAK 4; Serine/threonine protein kinase PAK4; Serine/threonine-protein kinase PAK 4
  • 種屬:
    Homo sapiens (Human)
  • 蛋白長度:
    Full Length of Isoform 2
  • 來源:
    E.coli
  • 分子量:
    63.9kDa
  • 表達區域:
    1-426aa
  • 氨基酸序列
    MFGKRKKRVEISAPSNFEHRVHTGFDQHEQKFTGLPRQWQSLIEESARRPKPLVDPACITSIQPGAPKTIVRGSKGAKDGALTLLLDEFENMSVTRSNSLRRDSPPPPARARQENGMPEKPPGPRSPQREPQRVSHEQFRAALQLVVDPGDPRSYLDNFIKIGEGSTGIVCIATVRSSGKLVAVKKMDLRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIAAVCLAVLQALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPRLKNLHKVSPSLKGFLDRLLVRDPAQRATAAELLKHPFLAKAGPPASIVPLMRQNRTR
    Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
    If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.
  • 蛋白標簽:
    N-terminal 6xHis-SUMO-tagged
  • 產品提供形式:
    Liquid or Lyophilized powder
    Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
  • 緩沖液:
    If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
    Note: If you have any special requirement for the glycerol content, please remark when you place the order.
    If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.
  • 儲存條件:
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保質期:
    The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
    Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
  • 貨期:
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
    Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
  • 注意事項:
    Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
  • Datasheet & COA:
    Please contact us to get it.

產品評價

靶點詳情

  • 功能:
    Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.
  • 基因功能參考文獻:
    1. These results implicate a novel role for PAK4 within the PI3K pathway via interaction with p85alpha. Thus, PAK4 could be an essential player in PDAC progression representing an interesting therapeutic opportunity. PMID: 28205613
    2. This review will discuss the emerging data highlighting the prominence of PAK4 in Pancreatic distal adenocarcinoma(PDAC) and its potential role for transforming patient management. PMID: 29508632
    3. this series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity PMID: 29443911
    4. X-ray crystallography reveals that in addition to the canonical PAK4 CDC42/RAC interactive binding (CRIB) domain binding to CDC42 there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42, and the PAK4 polybasic region. PMID: 29295922
    5. High PAK4 expression is associated with glioma. PMID: 28677773
    6. These results indicate that miR485 acts as a tumour suppressor in Glioblastoma (GBM) by, at least partially, directly targeting PAK4 and regulating the AKT and ERK signalling pathways. Thus, miR485 may be a potential target for the treatment of patients with GBM. PMID: 29048626
    7. Study reports the overexpression of PAK4 in neuroblastoma cells and, that PF-3758309, a potent PAK4 inhibitor, inhibits cell proliferation and survival in neuroblastoma cells via inhibition of the MEK/ERK pathway. These results suggest a role of PAK4 in neuroblastoma development. PMID: 29048629
    8. Methylation at cg14010619 may modify PAK4 activity, which has been implicated in cisplatin resistance in malignant cell lines PMID: 28444219
    9. PAK4 downregulated the level of p21 and enhanced the activity of Akt as well. And we conclude that PAK4 acts as a regulator of cell cycle progression of vascular smooth muscle cells by mediating Akt signaling and controlling p21 levels, which further modulate intimal hyperplasia and vascular smooth muscle cells proliferation PMID: 28706947
    10. Findings revealed a novel function of PAK4 in thyroid stimulating hormone-induced papillary thyroid cancer progression. PMID: 28178642
    11. The present study demonstrates that miR-145 plays an important role in inhibiting cell migration by directly targeting PAK4, and identifies miR-145-PAK4-LIMK1-cofilin as a novel regulatory pathway that contributed to colorectal cancer metastasis. PMID: 28440035
    12. These findings revealed a novel glucose metabolism-related mechanism of PAK4 in promoting colon cancer cell growth, suggesting that PAK4 and/or G6PD blockage might be a potential therapeutic strategy for colon cancer. PMID: 28542136
    13. PAK4 (but not PAK1) mediates invadopodia maturation during melanoma invasion likely via inhibition of PDZ-RhoGEF. PMID: 27765920
    14. these results indicate that PAK4 confers CDDP resistance via the activation of MEK/ERK and PI3K/Akt pathways. PAK4 and PI3K/Akt pathways can reciprocally activate each other. PMID: 27919028
    15. PAK4 activity was markedly decreased in postmortem brain tissue from Parkinson's disease (PD) patients and in rodent models of PD. Expression of constitutively active PAK4(S445N/S474E) (caPAK4) protected DA neurons in both the 6-hydroxydopamine and alpha-synuclein rat models of PD and preserved motor function. PMID: 27903866
    16. Our results indicate that PAK4 plays an important role in the potentiation of insulin secretion by fatty acids downstream of GPR40. PMID: 27700527
    17. PAK4 downregulation decreased PPARgamma-mediated Nox1 expression and suppressed EMT in IR-treated glioma cells. PMID: 28534509
    18. miR-1271/Zic2/PAK4 axis plays an important role in hepatocellular carcinoma progression. PMID: 28577975
    19. findings suggest that PAK4-activated PI3K/AKT signaling is both kinase-dependent and -independent, which contributes to breast cancer progression PMID: 28407679
    20. Functional role and therapeutic targeting of PAK4 in multiple myeloma has been presented. PMID: 28096095
    21. PAK4 overexpression in hepatocellular carcinoma (HCC) promotes metastatic invasion by regulating p53 phosphorylation. PMID: 27496712
    22. Study demonstrated that PAK4 interacted with eEF1A1 to promote migration and invasion of gastric cancer cells, thereby providing new insights into the function of PAK4 and eEF1A1 in the progression of gastric cancer. PMID: 28393218
    23. The results support a novel connection between HIF-1a and Pak4 in hypoxic cancer cells, and provide insights into mechanisms whereby tumors respond to and thrive under oxygen-deficient conditions. PMID: 28288786
    24. Data suggest that signaling via ANP/ANPR (atrial natriuretic factor/ANP receptor) in vascular endothelial cells activates PAK4 (p21-activated kinase 4) and CCM2 (cerebral cavernous malformation 2 protein), resulting in phosphorylation of MLC (myosin light chain), cytoskeletal reorganization, and cell spreading; kinase homology domain of ANPRA (guanylyl cyclase-A) activates downstream targets of ANP/ANPR signaling. PMID: 28432261
    25. High expression of PAK4 is associated with breast cancer. PMID: 27297086
    26. In gastric cancer, High PAK4 expression was significantly correlated with clinicopathological variables related to tumour progression, including depth of invasion, metastatic lymph nodes, pathological stage, distant metastasis or recurrent disease. High PAK4 expression was significantly associated with poorer disease-specific survival and relapse-free survival. PMID: 26614788
    27. PAK4 methylation by SETD6 promotes the activation of the Wnt/beta-catenin pathway. PMID: 26841865
    28. Study has confirms prognostic role of PAK4 level in cervical cancer patients and recognizes the regulatory role in cervical cancer progression. PAK4 also confers the chemoresistance of cervical cancer cells in a PI3K/Akt-dependent way. PMID: 26411419
    29. PAK4 catalytic domain binds cellular ATP and the Inka1 inhibitor. The crystal lattice consists only of PAK4-PAK4 contacts, which form a hexagonal array with channels of 80 A in diameter that run the length of the crystal. PMID: 26607847
    30. PAK4 localizes to cell-cell junctions and contributes to estblishing cell polarity.PAK4 phosphorylate beta-catenin Serine-675.PAK4 binding to cell-cell junctions is dependent on Cdc42. PMID: 26068882
    31. Nuclear Pak4 is involved in the pathogenesis of endometrial cancer especially in postmenopausal women. PMID: 26218748
    32. data show decreased nuclear accumulation and transcriptional activity of STAT3 in PAK4-silenced pancreatic cancer cells PMID: 26546043
    33. this report reveals that high level of p-Pak4 correlates with poor prognosis in gastric cancer (GC), thereby suggesting that p-Pak4 might be a potential prognostic marker for GC. PMID: 26124003
    34. PAK4 and RhoU cooperate to drive adhesion turnover and promote cell migration. PMID: 26598620
    35. PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC. PMID: 25975262
    36. CXCL12/CXCR4 signaling has a role in docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIMK1 PMID: 25359780
    37. microRNA-433 (miRNA-433 directly targets PAK4 through the miRNA-433 binding sequence at the 3'-UTR of PAK4 mRNA. PMID: 25410752
    38. PAK1 and PAK4 expression were associated with colorectal cancer metastasis and infiltration PMID: 25791829
    39. PAK4 promotes alpha-MSH/UVB-induced melanogenesis via the CREB and Wnt/beta-catenin signaling pathways and suggest that PAK4 may be a potential therapeutic target in pigmentation disorders. PMID: 25560280
    40. Suggest that PAK4 is a regulator of NF-kappaB pathway in pancreatic cancer cells, controlling cell proliferation and survival. PMID: 25238288
    41. PAK4 phosphorylates Par6B at Ser143 blocking its interaction with Cdc42. PMID: 25662318
    42. Increased Pak4 expression can lead to development of adenomyosis by enhancing the invasiveness of endometrial cells through regulation of MMP-2 and -9 activities. PMID: 25637478
    43. PAK4 is known to act as a transporter for beta-catenin nuclear translocation. PMID: 24829151
    44. p21-activated kinase 4 inhibitor PF-3758309 shows anti-metastatic effect. PMID: 24366569
    45. PAK4-SCG10 signaling occurs in gastric cancer cell invasion. PMID: 23893240
    46. The results document an oncogenic role of PAK4 in repression of Smad2/3 transactivation that involved in tumorigenesis, and suggest PAK4 as a potential therapeutic target for gastric cancer. PMID: 23934187
    47. Both indole and indazole of KY-04031 are responsible for PAK4 hinge interaction. PMID: 24704155
    48. Mutation of this residue was sufficient to switch the phosphorylation site preference for multiple kinases, including the serine-specific kinase PAK4 and the threonine-specific kinase MST4. PMID: 24374310
    49. Genotype TT for rs9676717 in PAK4 gene and no drinking may be predictive of the interferon-a treatment success. PMID: 23652058
    50. we confirmed that the mechanisms of the Pak4-induced cell cycle arrest invovlve the activation of the ATM/Chk1/2/p53 pathway. PMID: 23229348

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  • 亞細胞定位:
    Cytoplasm.
  • 蛋白家族:
    Protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily
  • 組織特異性:
    Highest expression in prostate, testis and colon.
  • 數據庫鏈接:

    HGNC: 16059

    OMIM: 605451

    KEGG: hsa:10298

    STRING: 9606.ENSP00000351049

    UniGene: Hs.20447



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