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GPCRs: Exploring New Paradigms

As one of the largest and most diverse protein families in nature, the G-protein coupled receptor (GPCR) superfamily play important roles in a variety of biological and pathological processes such as development and proliferation, neuromodulation, angiogenesis, metabolic disorders, inflammation, and viral infection. Not surprisingly, it is one of the most targeted protein families in pharmaceutical research today (Schlyer 2006).

All members of this superfamily share a similar seven transmembrane domain, but are grouped on the basis of shared sequence motifs into the following broad classes:

Class A Rhodopsin-like
Class B Secretin-like
Class C Metabotropic glutamate/pheromone
Class D Fungal pheromone
Class E cAMP receptors
Vomeronasal receptors

The pharmaceutical industry has focused on development of modulators to this protein family, but GPCRs also represent an attractive target as biomarkers. Recent studies have implicated endothelin receptors, chemokine receptors and lysophosphatidic acid receptors in tumorgenesis and metastasis, and a recent in silico analysis found a number of GPCRs that were up-regulated in various cancers which suggests not only targets of therapeutic value, but of diagnostic and prognostic value as well. A summary of these up-regulated receptors is below.

Lung cancer
Edg2, P2Y purinoceptor 6, PAR-2, PAR-3, GPR68
Breast cancer
Prostate cancer
Beta 2 adrenergic receptor, CXCR-3, CXCR-4, GPR68
Edg6, PAR-2, mGluR1
Gastric cancer
CXCR-4, P2Y purinoceptor 5
Beta 2 adrenergic receptor, Edg1, CCR7

While research continues, it is evident that GPCRs are critical in countless biological functions--and disfunctions. While the emphasis is on their role in drug development, it is becoming increasingly clear that G-protein coupled receptors will play a critical role as indicators of disease with diagnostic and prognostic potential. IMGENEX carries over 900 IHC, WB, and flow validated GPCR antibodies. View our complete GPCRs antibody list grouped by class and family. Also see our complete list of Tissue Microarray slides--perfect for GPCR localization.

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