Unlocking the Potential of PAK2 as a Drug Target and Biomarker

Target Name: PAK2

NCBI ID: G5062

PAK2

Unlocking the Potential of PAK2 as a Drug Target and Biomarker

Serine/threonine-protein kinase (PAK) 2 is a key regulator of cell proliferation, differentiation, and survival. The loss of PAK2 activity has been implicated in various diseases, including cancer, neurodegenerative disorders, and developmental defects. As a result, targeting PAK2 has become an attractive research focus with the potential to uncover new therapeutic approaches. In this article, we will explore the biology of PAK2, its role in disease, and the prospects of PAK2 as a drug target and biomarker.

Biography of PAK2

PAK2 is a 21-kDa protein that is primarily located in the cytoplasm. It is composed of a 21 kDa catalytic protein and a 140 amino acid carboxy-terminal tail. The catalytic protein consists of a 110 amino acid N-terminal region, a 35 amino acid catalytic region, and a 35 amino acid C-terminal region. The carboxy-terminal tail contains a single amino acid that is involved in protein-protein interactions.

PAK2 functions as a negative regulator of the RhoA GTPase, which is a critical regulator of cell proliferation and differentiation. RhoA GTPase is activated by various growth factors, including PDGF, and in response, it regulates the association of PAK2 to the RhoA protein. This association is necessary for PAK2 to regulate the activity of multiple downstream targets, including the transcription factor, NF-kappa-B, and the tyrosine kinase Yes/TAZ.

Diseases associated with PAK2

The loss of PAK2 activity has been implicated in various diseases, including cancer, neurodegenerative disorders, and developmental defects. One of the most well-documented examples is the loss of PAK2 activity in neurodegenerative disorders, including Alzheimer's disease. In Alzheimer's disease, the levels of PAK2 are reduced, and the levels of RhoA are increased, which results in the misregulation of the neurotransmitter, 尾-amyloid, and the neurotoxin, tau.

Another example is the loss of PAK2 activity in cancer. Many studies have shown that the levels of PAK2 are increased in various types of cancer, including breast, lung, and ovarian cancer. The increased levels of PAK2 have been associated with the resistance of cancer cells to chemotherapy and the development of drug resistance.

In addition to these examples, PAK2 has also been implicated in various other diseases, including heart disease, diabetes, and respiratory disorders. The exact mechanisms by which PAK2 is involved in these diseases are not yet fully understood, but it is clear that its loss or dysfunction has significant implications for human health.

Potential of PAK2 as a drug target

The loss of PAK2 activity has led to the interest in targeting this protein as a potential drug target. Several studies have shown that inhibiting the activity of PAK2 can lead to the inhibition of various cellular processes, including cell proliferation, migration, and invasion. In addition, PAK2 has been shown to play a role in the development of drug resistance in cancer cells, which could make it an attractive target for anti-cancer agents.

One of the most promising strategies for targeting PAK2 is the use of small molecules that can inhibit its activity. Several studies have shown that inhibitors of PAK2, such as paclitaxel and nilotinib, can significantly reduce the levels of PAK2 in cancer cells. These inhibitors work by binding to specific sites on PAK2, leading to the inhibition of its activity.

Another approach to targeting PAK2 is the use of monoclonal antibodies (mAbs) that are specific for PAK2. These antibodies can be used to

Protein Name: P21 (RAC1) Activated Kinase 2

Functions: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:7744004, PubMed:19273597, PubMed:19923322, PubMed:9171063, PubMed:12853446, PubMed:16617111, PubMed:33693784). Acts as downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:9171063, PubMed:12853446, PubMed:16617111). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964)

The "PAK2 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about PAK2 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

More Common Targets