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Rabbit Anti-Phospho-PAK1 + PAK2 + PAK3 (T423 + T402 + T421)/FITC Conjugated antibody
background:
In mammals, there are several identified isoforms of p21 Activated Protein Kinases or PAKs: PAK1 and PAK3 are mostly brain specific, while PAK2 is expressed ubiquitously. Mutations of the gene coding for PAK3 are associated with X linked mental retardation and PAK3 is a key regulator of synapse formation and plasticity in the hippocampus. PAK3 is thought to play a key role in regulation of cell shape and motility as well as cell death. P21-activated kinase (PAK) is actually a family of serine/threonine protein kinases, members of which are activated by small molecular weight GTPases. The three most common isoforms are PAK 1, PAK 2, and PAK 3 (also known as alpha PAK, gamma PAK, and beta PAK, respectively). These kinases contain numerous regulatory elements that trigger diverse signaling processes such as those initiated by activated GTPases, interaction with Src homology 3 (SH3) domains, and caspase mediated proteolytic cleavage. Autophosphorylation of serine 141 (serine 144 for PAK 1 and serine 139 PAK 3), catalyzed by Cdc42, is required for activation of PAK.
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. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2.
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. Interacts with ARHGEF7. Also interacts with CRIPAK. Interacts with NISCH. Interacts with DVL1; mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM (via cytoplasmic domain); the interaction is direct and enhanced in presence of RAC1. Interacts with SCRIB. Interacts with PDPK1. Interacts (via kinase domain) with RAF1. Interaction with NCK1 and NCK2.
Subcellular Location:
Cytoplasm. Cell junction, focal adhesion. Note=Recruited to focal adhesions upon activation.
Post-translational modifications:
Autophosphorylated when activated by CDC42/p21 and RAC1. Phosphorylation at Thr-423 by PDPK1 results in its activation.
Similarity:
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Contains 1 CRIB domain.
Contains 1 protein kinase domain.
Database links:
Entrez Gene: 5058 Human
Entrez Gene: 18479 Mouse
Entrez Gene: 29431 Rat
Omim: 602590 Human
SwissProt: Q13153 Human
SwissProt: O88643 Mouse
SwissProt: P35465 Rat
Unigene: 435714 Human
Unigene: 260227 Mouse
Unigene: 9149 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
PAK1-3蛋白具有广泛的生物学功能,也是一个保守的丝氨酸/苏氨酸蛋白激酶,参与许多重要的细胞活动。包括细胞骨架的动力学调节,细胞移动,生存和凋亡,细胞周期,基因转录调节,细胞生长信号转导和转化等。
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