Cell Biology

The cell cycle is an ordered set of events by which cells undertake growth and division into two daughter cells. In eukaryotes, the cell cycle is described by five phases: G0, G1, S, G2, and M. In G0 phase, cells have entered a quiescent state or are not dividing. During G1 period, the cells grow and accumulate nutrients for the subsequent S phase, where DNA replication occurs. The gap between S and M phases is termed G2 period, during which the cells continue to grow and prepare for mitosis that occurs in M phase. All these processes are elaborately controlled to ensure proper cell development and renewal. The key molecules that program cell cycle are cyclins and cyclin-dependent kinases (CDKs), whereas inhibitors that prevent improper cell division are two families of genes, the Cip / Kip family and the INK4 family. Notably, these inhibitor genes are also termed tumor suppressor genes as they are instrumental in the prevention of tumor formation.

Cell death occurs when a cell is no longer able to sustain essential life functions. Cells can die through one of several biochemically distinct pathways, with apoptosis and necrosis being the two most commonly studied mechanisms. While the term “autophagic cell death” would suggest death by autophagy, this form of cell killing occurs only in specific cases, as autophagy is generally considered a pro-survival process. Aside from these three modalities, other forms of cell death described by terms such as “mitotic catastrophe” or “excitotoxicity” are present in the literature. However, more research will have to be done to determine whether these and other named processes truly represent distinct death pathways.

C Reactive Protein antibody (GTX101262)

Autophagy has been implicated in many different diseases, including neurodegeneration, cardiac myopathy, autoimmune disease and cancer. The role of autophagy in cancer is complex and paradoxical. While autophagic deficiency has been shown to promote tumorigenesis in animal models, autophagy may actually support tumor growth by enhancing cancer cell survival in the face of nutrient depletion or accumulation of toxic molecules. GeneTex is proud to introduce our antibodies for autophagy research.

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DFNA5 antibody

Cat No. GTX64590

DFNA5 antibody, N-term

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DFNA5 antibody, C-term

Cat No. GTX46489

The subcellular location of a protein may suggest potential roles for that factor in one or more cellular processes. Organelle protein-specific antibodies are essential for establishing colocalization of a particular protein of interest with an organelle, thereby contributing crucial insight into its possible function(s). In addition, these organelle marker antibodies can often be used in cell fractionation studies analyzed by western blot alone or after immunoprecipitation.

Cytosol

Endoplasmic Reticulum (ER)

Pyroptosis is a programmed cell death process executed by inflammatory caspases upon initiation of canonical or non-canonical mechanisms. It is triggered by specific inflammatory caspases (caspase-1, -4, -5, -11) that are distinct from those responsible for apoptosis. Both the canonical and non-canonical pathways lead to the activation of gasdermin D (GSDMD), which forms pores that cause cellular leakage and lysis. The canonical sequence involves pathogen-associated molecular patterns (PAMPs)- and damage-associated molecular patterns (DAMPs)-mediated inflammasome formation leading to caspase-1 activation, GSDMD cleavage, and IL-1β and IL-18 maturation. The non-canonical string of events is characterized by direct interaction of the other three caspases with Gram-negative bacterial lipopolysaccharide (LPS) with subsequent GSDMD activation. The resultant extracellular release of cytoplasmic components unleashes a local inflammatory cascade that can become systemic, underscoring the importance of pyroptosis’ normal function in mobilizing immune cells against pathogens. Nevertheless, pyroptosis can also contribute to inflammation-related pathology, including cancer progression and autoimmune disease.

GeneTex is proud to offer an outstanding selection of antibodies to study pyroptosis and inflammation biology. These antibodies are validated for various applications to facilitate your efforts in this exciting field. Please see the highlighted products below

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G protein-coupled receptors (GPCRs) constitute the largest superfamily of human cell surface transmembrane receptors with over 820 genes. They respond to a variety of ligands that include hormones, neurotransmitters, metabolites, ions, photons, and mechanical forces, with subsequent intracellular signaling relayed through G protein-dependent and -independent mechanisms. GPCR-triggered pathways are responsible for a plethora of physiological and pathophysiological effects, which is why approximately a third of all prescribed drugs target their activity. Of the more than 350 human GPCRs that are not sensory receptors, perhaps 140 are considered “orphan” receptors with no known ligand or function. Emphasizing their clinical value, it is thought that ~60-85% of potentially therapeutic GPCRs have no drugs directed at them.

GeneTex is committed to establishing the most extensive product line of antibodies for human GPCRs, with all new production being recombinant monoclonal antibodies. These antibodies will be thoroughly characterized through enhanced “Five Pillar” validation strategies that feature knockdown/knockout lysates, comparable antibodies, cell fractionation, detection of endogenous GPCR expression, and overexpression. In addition, specialized testing using human GPCR arrays will be utilized when feasible. The goal is to generate the most diverse, expansive, and meticulously verified antibody reagents for GPCR biology research.

GPCRs play a crucial role in the regulation of tissue/cell physiology and homeostasis in the immune, nervous, endocrine, and cardiovascular systems, among others. They also function in a multitude of pathological processes, including cancer.

GPCRs in cancers

Many GPCRs serve as potential biomarkers for early cancer diagnosis. Furthermore, GPCRs are active in various aspects of cancer progression, including proliferation, apoptosis, angiogenesis, migration, and invasion. Therefore, the pharmacological inhibition of GPCRs and their downstream targets presents a promising avenue for developing novel, mechanism-based strategies for cancer therapy.

GPCRs in the immune system

Inflammatory cells such as leukocytes, monocytes, macrophages, and dendritic cells express more than one GPCR and sense a wide range of chemoattractants and chemokines. These receptors are crucial for the migration and infiltration of immune cells. Abnormal GPCR expression can lead to immune system dysfunction manifesting as inflammatory and autoimmune disease.

GPCRs in the nervous system

The nervous system utilizes membrane receptors to detect extracellular stimuli. By expressing GPCRs with diverse ligand-recognition capabilities, the nervous system can selectively filter and respond to specific signals. GPCRs are involved in chronic neurodegenerative diseases including but not limited to Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease.

GPCRs in homeostasis

GPCRs play a crucial role in maintaining metabolic balance by influencing key processes such as glucose homeostasis and insulin secretion, appetite, calcium sensing, heart rate, and blood pressure.

Table 1. GPCRs related to different disorders

GPCRs share structural characteristics that include seven transmembrane (7TM) domains linked by both intra- and extracellular loops, an extracellular N-terminus, and an intracellular C-terminus. The loops, as well as the intra- and extracellular domains, are all subject to post-translational modifications. One widely used GPCR classification system is based on sequence homology and evolutionary relationships. This organizes GPCRs into six families designated A-F.

Table 2. GPCR families

 Class A

GPCR signaling begins with engagement of the receptor by a ligand, which leads to allosteric changes in the intracellular domains of the GPCR. In general, two types of effectors can then associate with the GPCR: (a) a Gα subunit that complexes with β and γ subunits to form the G protein trimer, and (b) β-arrestins that can direct their own signaling. It is becoming clear that GPCR signaling emanates not only from the cell surface but also from other intracellular compartments (e.g., endosomes, the Golgi apparatus, and the ER, among others). Signaling cascades involving kinases and transcription factor regulation orchestrate the subsequent cellular response.

Classically, GPCR signaling undergoes termination through GTP hydrolysis and dissociation of Gα-Gβγ. G protein-coupled receptor kinases (GRKs) phosphorylate the C-terminal tail of GPCRs, facilitating the binding of the β-arrestins that, as mentioned above, can trigger their own signaling as well as contribute to GPCR desensitization and internalization. The GRK family, comprising seven kinases (GRK1-7), is categorized into three subfamilies: (1) the GRK1 subfamily consists of rhodopsin kinase (GRK1) and GRK7, (2) the GRK2 subfamily consists of β-adrenergic receptor kinase-1 and -2 (GRK2 and GRK3), and (3) the GRK4 subfamily consists of GRK4-6. GRK2, GRK3, GRK5, and GRK6 are key regulators of GPCRs. Beyond GRKs and arrestins, GPCR functions and signal transduction are influenced by GPCR-interacting proteins (GIPs) such as receptor activity-modifying proteins (RAMPS), regulators of G protein signaling (RGS) proteins, GPCR-associated sorting proteins (GASPs), Homer proteins, and PDZ-scaffold proteins.

Table 3. mRNA Expression of GRKs and β-arrestins in tissues

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