Anti- PAK1 (Phospho-Thr212) 抗体

Binding Site: Thr212

Description: Antibodies were produced by immunizing rabbits with synthetic phosphopeptide and KLH conjugates. Antibodies were purified by affinity-chromatography using epitode-specific phosphopeptide. Non-phospho specific antibodies were removed by chromatogrmphy using non-phosphopeptide.

WB Dilution: 500~1000

IHC Dilution: 50~100

Immunogen: Peptide sequence around phosphorylation site of threonine 212 (P-V-T(p)-P-T) derived from Human PAK1.

Immunofluorescence: 1:100 ~ 1:200

Citation: 1: Karjalainen M, Kakkonen E, Upla P, Paloranta H, Kankaanpää P, Liberali P, Renkema GH, Hyypiä T, Heino J, Marjomäki V. A Raft-derived, Pak1-regulated entry participates in alpha2beta1 integrin-dependent sorting to caveosomes. Mol Biol Cell. 2008 Jul;19(7):2857-69. Epub 2008 Apr 30. PubMed PMID: 18448666; PubMed Central PMCID: PMC2441652

Function: The activated kinase acts on a variety of targets. Likely to be the GTPase effector that links the Rho-related GTPases to the JNK MAP kinase pathway. Activated by CDC42 and RAC1. Involved in dissolution of stress fibers and reorganization of focal complexes. Involved in regulation of microtubule biogenesis through phosphorylation of TBCB. Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2.

Catalytic Activity: ATP + a protein = ADP + a phosphoprotein.

Cofactor: Magnesium.

Enzyme Regulation: Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-423 and allows the kinase domain to adopt an active structure. Also activated by binding to GTP-bound CDC42, independent of the phosphorylation state of Thr-423. Phosphorylation of Thr-84 by OXSR1 inhibits this activation (By similarity).

Subunit: Homodimer in its autoinhibited state. Active as monomer. Interacts tightly with GTP-bound but not GDP-bound CDC42/P21 and RAC1. Binds to the caspase-cleaved p110 isoform of CDC2L1 and CDC2L2, p110C, but not the full-length proteins. Component of cytoplasmic complexes, which also contain PXN, ARHGEF6 and GIT1.

Subcellular Location: Cytoplasm. Cell junction, focal adhesion. Note=Recruited to focal adhesions upon activation.

Ptm: Autophosphorylated when activated by CDC42/p21 and RAC1.

Similarity: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Similarity: Contains 1 CRIB domain.

Similarity: Contains 1 protein kinase domain.

[1] Brown J.L., Stowers L., Baer M., Trejo J., Coughlin S., Chant J.
Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway.
[2] Sells M.A., Knaus U.G., Bagrodia S., Ambrose D.M., Bokoch G.M., Chernoff J.
Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells.
[3] Reid T., Aspenstroem P., Bertoglio J.
Human PAK1B.
[4] Manser E., Huang H.Y., Loo T.H., Chen X.Q., Dong J.M., Leung T., Lim L.
Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes.
[5] Frost J.A., Khokhlatchev A., Stippec S., White M.A., Cobb M.H.
Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation.
[6] Zhao Z.S., Manser E., Chen X.Q., Chong C., Leung T., Lim L.
A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1.
[7] Zenke F.T., King C.C., Bohl B.P., Bokoch G.M.
Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity.
[8] Parrini M.C., Lei M., Harrison S.C., Mayer B.J.
Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1.
[9] Chen S., Yin X., Zhu X., Yan J., Ji S., Chen C., Cai M., Zhang S., Zong H., Hu Y., et al.
The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis.
[10] Vadlamudi R.K., Barnes C.J., Rayala S., Li F., Balasenthil S., Marcus S., Goodson H.V., Sahin A.A., Kumar R.
p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B.

Product Protocol: To see this product used in a peer reviewed journal, click the following link:
A Raft-derived, Pak1-regulated Entry Participates in α2β1 Integrin-dependent Sorting to Caveosomes