LPAR1
Description
The LPAR1 (lysophosphatidic acid receptor 1) is a protein-coding gene located on chromosome 9.
Lysophosphatidic acid receptor 1, also known as LPA1, is a protein that in humans is encoded by the LPAR1 gene. LPA1 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). The integral membrane protein encoded by this gene is a lysophosphatidic acid (LPA) receptor from a group known as EDG receptors. These receptors are members of the G protein-coupled receptor superfamily. Utilized by LPA for cell signaling, EDG receptors mediate diverse biologic functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. Alternative splicing of this gene has been observed and two transcript variants have been described, each encoding identical proteins. An alternate translation start codon has been identified, which results in isoforms differing in the N-terminal extracellular tail. In addition, an alternate polyadenylation site has been reported. LPAR1 gene has been detected progressively overexpressed in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, this gene is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.
LPAR1 is a receptor for lysophosphatidic acid (LPA), a lipid signaling molecule. It plays a crucial role in various cellular processes including cytoskeleton reorganization, cell migration, differentiation, and proliferation, contributing to responses to tissue damage and infections. LPAR1 activates downstream signaling cascades through G protein families, leading to inhibition of adenylyl cyclase activity, decreased cAMP levels, and increased cytoplasmic Ca(2+) levels. It also activates RALA, initiating phospholipase C activation and inositol 1,4,5-trisphosphate production. LPAR1 is involved in regulating cell shape, promoting Rho-dependent cytoskeletal reorganization and actin stress fiber formation in neurons. It facilitates lamellipodia formation during cell migration through RAC1 activation. Acting as an LPA receptor, LPAR1 plays a role in chemotaxis and cell migration, including wound healing responses. It contributes to inflammation triggered by bacterial lipopolysaccharide (LPS) through interaction with CD14. LPAR1 promotes cell proliferation in response to LPA and inhibits intracellular ciliogenesis through AKT1 activation. It is essential for normal skeleton development, potentially involved in osteoblast differentiation, and critical for normal brain development. LPAR1 is required for the normal proliferation, survival, and maturation of newly formed neurons in the adult dentate gyrus. It is implicated in pain perception and neuropathic pain initiation. LPAR1 interacts with RALA, GRK2, GNAQ, GNA13, and CD14, with its interaction with CD14 enhanced by LPS exposure.
LPAR1 is also known as EDG2, Gpcr26, LPA1, Mrec1.3, VZG1, edg-2, rec.1.3, vzg-1.
