CXCL1

CXCL1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1MGS, 1MSG, 1MSH
Identifiers
Aliases	CXCL1, FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3, SCYB1, C-X-C motif chemokine ligand 1
External IDs	OMIM: 155730 HomoloGene: 136748 GeneCards: CXCL1
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q13.3 Start 73,869,393 bp[1] End 73,871,308 bp[1]
RNA expression pattern Bgee Top expressed in smooth muscle tissue islet of Langerhans palpebral conjunctiva spleen lung synovial membrane periodontal fiber More reference expression data BioGPS n/a
Gene ontology Molecular function signaling receptor binding growth factor activity cytokine activity GO:0010577 enzyme activator activity CXCR chemokine receptor binding chemokine activity Cellular component extracellular region extracellular space specific granule lumen tertiary granule lumen Biological process negative regulation of cell population proliferation GO:0007243 intracellular signal transduction response to lipopolysaccharide signal transduction G protein-coupled receptor signaling pathway nervous system development positive regulation of neutrophil chemotaxis cell population proliferation actin cytoskeleton organization immune response chemokine-mediated signaling pathway GO:0048554 positive regulation of catalytic activity cell chemotaxis chemotaxis defense response inflammatory response neutrophil degranulation antimicrobial humoral immune response mediated by antimicrobial peptide regulation of signaling receptor activity cytokine-mediated signaling pathway neutrophil chemotaxis leukocyte chemotaxis cellular response to lipopolysaccharide Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2919	n/a
Ensembl	ENSG00000163739	n/a
UniProt	P09341	n/a
RefSeq (mRNA)	NM_001511	n/a
RefSeq (protein)	NP_001502	n/a
Location (UCSC)	Chr 4: 73.87 – 73.87 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils^[3][4] or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. It was previously called GRO1 oncogene, GROα, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). It's also known as keratinocytes-derived chemokine (KC) in mice or cytokine-induced neutrophil chemoattractant type-1 (CINC-1) in rats. In humans, this protein is encoded by the gene Cxcl1 ^[5] and is located on human chromosome 4 among genes for other CXC chemokines.^[6]

Structure and expression[]

CXCL1 exists as both monomer and dimer and both forms are able to bind chemokine receptor CXCR2.^[7] However, CXCL1 chemokine is able to dimerize only at higher (micromolar) concentrations and its concentrations are only nanomolar or picomolar upon normal conditions, which means that the form of WT CXCL1 is more likely monomeric while dimeric CXCL1 is present only during infection or injury. CXCL1 monomer consists of three antiparallel β-strands followed by C- terminal α-helix and this α-helix together with the first β-strand are involved in forming a dimeric globular structure.^[8]

Upon normal conditions, CXCL1 is not expressed constitutively. It's produced by a variety of immune cells such as macrophages, neutrophils and epithelial cells,^[9][10] or Th17 population. Moreover, its expression can be also induced indirectly by IL-1, TNF-α or IL-17 produced again by Th17 cells ^[11] and is triggered mainly by activation of NF-κB or C/EBPβ signaling pathways predominantly involved in inflammation and leading to production of other inflammatory cytokines.^[11]

Function[]

CXCL1 has a potentially similar role as interleukin-8 (IL-8/CXCL8). After binding to its receptor CXCR2, CXCL1 activates phosphatidylinositol-4,5-bisphosphate 3-kinase-γ (PI3Kγ)/Akt, MAP kinases such as ERK1/ERK2 or phospholipase-β (PLCβ) signaling pathways. CXCL1 is expressed at higher levels during inflammatory responses thus contributing to the process of inflammation.^[12] CXCL1 is also involved in the processes of wound healing and tumorigenesis.^[13][14][15]

Role in cancer[]

CXCL1 has a role in angiogenesis and arteriogenesis ^[16] and thus has been shown to act in the process of tumor progression. The role of CXCL1 was described by several studies in the development of various tumors, such as breast cancer, gastric and colorectal carcinoma or lung cancer.^[17][18][19] Also, CXCL1 is secreted by human melanoma cells, has mitogenic properties and is implicated in melanoma pathogenesis.^[20][21][22]

Role in nervous system and sensitization[]

CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors.^[7] CXCR2 receptor for CXCL1 is expressed in the brain and spinal cord by neurons and oligodendrocytes and during CNS pathologies such as Alzheimer's disease, multiple sclerosis and brain injury also by microglia. An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function.^[23] On the other hand, on the periphery, CXCL1 contributes to the release of prostaglandins and thus causes increased sensitivity to pain and drives nociceptive sensitization via recruitment of neutrophils to the tissue. Phosphorylation of ERK1/ERK2 kinases and activation of NMDA receptors leads to transcription of genes inducing chronic pain, such as c-Fos or cyclooxygenase-2 (COX-2).^[12]

References[]

External links[]

• Human CXCL1 genome location and CXCL1 gene details page in the UCSC Genome Browser.