The Function of PAK1
Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that 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. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321).
Protein names
Recommended name:
Serine/threonine-protein kinase PAK 1Short name:
PAK-1Alternative name(s):
Alpha-PAKp21-activated kinase 1
p65-PAK
- RS527589 (PAK1) ??
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Top Gene-Substance Interactions
PAK1 Interacts with These Diseases
| Disease | Score |
Substances That Increase PAK1
| Substances | Interaction | Organism | Category |
Substances That Decrease PAK1
| Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
|---|
Conditions with Decreased Gene Activity
| Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Overexpressed in gastric cancer cells and tissues (at protein level) (PubMed:25766321).
Gene Pathways:
- Immune System
- MAPK signaling pathway
- Regulation of actin cytoskeleton
- Signal Transduction
- Natural killer cell mediated cytotoxicity
- Cell-Cell communication
- Axon guidance
- Chemokine signaling pathway
- T cell receptor signaling pathway
- Epithelial cell signaling in Helicobacter pylori infection
- Renal cell carcinoma
Enzyme Regulation:
Phosphorylation of Thr-84 by OXSR1 inhibits activation (By similarity). Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, and enables activation by phosphorylation of Thr-423.
Molecular Function:
- Chromatin Binding
- Protein Serine/Threonine Kinase Activity
- Protein Kinase C Activity
- Signal Transducer, Downstream Of Receptor, With Serine/Threonine Kinase Activity
- Protein Kinase C Binding
- Collagen Binding
- Atp Binding
- Gtp-Rho Binding
- Ligand-Dependent Nuclear Receptor Transcription Coactivator Activity
- Histone Kinase Activity (H3-T11 Specific)
- Histone Binding
- Histone Deacetylase Binding
- Rac Gtpase Binding
- Androgen Receptor Binding
Biological Processes:
- Response To Hypoxia
- B Cell Homeostasis
- B Cell Apoptotic Process
- Positive Regulation Of Protein Phosphorylation
- Stimulatory C-Type Lectin Receptor Signaling Pathway
- Regulation Of Germinal Center Formation
- Regulation Of Immunoglobulin Production
- Renal System Process
- Transcription, Dna-Templated
- Regulation Of Transcription From Rna Polymerase Ii Promoter
- Protein Phosphorylation
- Negative Regulation Of Protein Kinase Activity
- Exocytosis
- Apoptotic Process
- Hyperosmotic Response
- Signal Transduction
- Activation Of Jun Kinase Activity
- Axonogenesis
- Positive Regulation Of Cell Proliferation
- Epithelial Cell Migration
- Peptidyl-Serine Phosphorylation
- Positive Regulation Of Cell Migration
- Negative Regulation Of B Cell Proliferation
- T Cell Costimulation
- Actin Cytoskeleton Reorganization
- Cellular Response To Insulin Stimulus
- Positive Regulation Of Peptidyl-Serine Phosphorylation
- Positive Regulation Of Intracellular Estrogen Receptor Signaling Pathway
- Histone H3-T11 Phosphorylation
- Fc-Epsilon Receptor Signaling Pathway
- Fc-Gamma Receptor Signaling Pathway Involved In Phagocytosis
- Wound Healing
- Positive Regulation Of Jun Kinase Activity
- Protein Autophosphorylation
- Ephrin Receptor Signaling Pathway
- Spleen Development
- Branching Morphogenesis Of An Epithelial Tube
- Neuron Projection Morphogenesis
- T Cell Receptor Signaling Pathway
- Positive Regulation Of Stress Fiber Assembly
- Negative Regulation Of Cell Proliferation Involved In Contact Inhibition
- Regulation Of Cell Motility