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SIGNALLING WAYS

chemokine NTD
chemokine subclass
chemokine name(s)
producer cell(s)
chemokine GPCR(s)
a-chemokines : CXC motif (on Homo 4q12-21 chromosome region) ELRCXC or ELR+ CXC chemokines (chemotactic for neutrophils) CXCL1 / KC / MGSA-a / GRO-1 / GRO-a (GRO-KC in mouse) activated granulocytes, monocytes, macrophages, epithelial cells, lymphatic endothelial cells (LEC) CXCR2 / CDw128b / IL-8RB >> CXCR1 / CDw128a / IL-8RA
Duffy antigen-related receptor for chemokines (DARC) (decoy)
CXCL2 / GRO-2 /  GRO-b / MGSA-b / MIP-2a (GRO-KC in mouse) activated granulocytes, monocytes, macrophages CXCR2 / CDw128b / IL-8RB
CXCL3 / GRO-3 / GRO-g / MGSA-g / MIP-2b (GRO-KC in mouse)
CXCR2 / CDw128b / IL-8RB
CXCL5 / ENA-78 (LIX in mouse)
CXCR1 / CDw128a / IL-8RA
CXCR2 / CDw128b / IL-8RB
Duffy antigen-related receptor for chemokines (DARC) (decoy)
CXCL6/ GCP-2 (Cka-3 in mouse)
CXCR1 / CDw128a / IL-8RA
CXCR2 / CDw128b / IL-8RB
CXCL7 / LDGF-PBP / NAP-2 / CTAP-II (from proteolytic truncation of connective tissue-activating peptide III (CTAP-III) (one of several molecular variants of -thromboglobulin-antigen (TG-Ag), a group of chemokines that differ by their degree of N-terminal truncation) by removing a stretch of 15 amino acids from the N terminus of the precursorref1, ref2. So far all evidence suggests that cell surface–bound cathepsin G (CathG), a chymotryptic serine protease also found in primary neutrophil granules, is responsible for CTAP-III processingref1, ref2, ref3, ref4. Among blood cells, only monocytes share the ability of neutrophils to convert CTAP-III into NAP-2ref1, ref2, albeit to a considerably lower extent than neutrophils, which argues against a relevant role for monocytes in NAP-2 formation during early inflammationref. Unstimulated MCs exceed the CTAP-III–processing potency of neutrophils about 30-fold thanks to chymase, whereas MCs activated by IgE cross-linking exhibit even 1000-fold higher CTAP-III–processing capacity than fMLP-stimulated neutrophils. Intriguingly, PF-4 counteracted MC- as well as neutrophil-mediated NAP-2 generation at physiologically relevant concentrationsref) a-granules of activated human platelets CXCR1 / CDw128a / IL-8RAref
CXCR2 / CDw128b / IL-8RBref
CXCL8 / IL-8 / NAP-1 / TCF / NAF / neutrophil chemotactic factor (NCF) alveolar macrophage, sweat CXCR1 / CDw128a / IL-8RA
CXCR2 / CDw128b / IL-8RB
Duffy antigen-related receptor for chemokines (DARC) (decoy)
XXXCXC or ELR- CXC chemokines (chemotactic for lymphocytes; PF4 very efficiently stimulates firm adhesion of neutrophils to endothelial cells as well as the selective exocytosis of secondary granule markersref1, ref2) CXCL4 / PF4 megakaryocytes, activated platelets a cell surface–expressed chondroitin sulfate proteoglycanref1, ref2
CXCL9 / monokine induced by IFN-g (MIG / MIG-1) (catabolysed by CD26 / DPPIV) monocytes, macrophages, T lymphocytes, fibroblasts, lymphatic endothelial cells (LEC) CXCR3 / CD183
CXCL10  / IP-10 (catabolysed by CD26 / DPPIV) monocytes, macrophages, T lymphocytes, fibroblasts, epithelial cells (including endothelial cells), lymphatic endothelial cells (LEC) CXCR3 / CD183
CXCL11 / IFN-inducible T cell a chemoattractant (I-TAC) / H174 (catabolysed by CD26 / DPPIV)
CXCR3 / CD183
CXCL12 / pre-B cell growth-stimulating factor (PBSF) / stromal cell-derived factor 1a (SDF-1a/b) (catabolysed by  by marrow serine proteasesref1, ref2 and dipeptidylpeptidase IV (CD26)ref1, ref2) fibroblasts, HIV-1 infected macrophages CD184 / CXCR4 / fusin / LESTR
CXCL13 / BCA-1 / BLC FDC CD195 / CXCR5 / BLR-1
CXCL16 / BUNZO / STRC33 / scavenger receptor PSOX (SR-PSOX) APC (also membrane bound) CXCR6
chemotactic for monocytes only CXCL14 / BMAC / BRAK / MIP-2g / bolekine / KEC / KS1 / NJAC
?

CXCL15 / lungkine in mouse
CD195 / CCR5 / BLR-1
b-chemokines : CC motif (on Homo 17q11-32 chromosome region; chemotactic for monocytes and plasma cells) CCL1 / I-309 (TCA-3 / P500 in mouse) activated T lymphocytes CCR8
CCL2 / MCF / MCAF / monocyte chemoattractant protein (MCP) / MCP-1 (JE in mouse) epithelial cell, fibroblast, smooth muscle cells, monocytes, alveolar macrophage, lymphatic endothelial cells (LEC) CCR2
Duffy antigen-related receptor for chemokines (DARC) (decoy)
D6 / chemokine binding protein 2 (CBBP) (decoy)
CCL3 / LD78 / MIP-1a (catabolysed by CD26 / DPPIV) epithelial cells, monocytes, macrophages, T lymphocytes CCR1
CD195 / CCR5 / BLR-1
CCL3L1
CD195 / CCR5 / BLR-1
CCR9
CCL4 / AT744.1 / LAG-1 / MIP-1b monocytes, macrophages, T lymphocytes CCR1
CD195 / CCR5 / BLR-1
CCL5 / RANTES (catabolysed by CD26 / DPPIV) T lymphocytes, activated NKT lymphocytes, epithelial cell, smooth muscle cell,eosinophils, monocytes, macrophages, fibroblast, lymphatic endothelial cells (LEC) CCR1
CCR3
CD195 / CCR5 / BLR-1
Duffy antigen-related receptor for chemokines (DARC) (decoy)
CCL6 (C10 / MRP-1 in mouse) , lymphatic endothelial cells (LEC) ?
CCL7 / MCP-3 (MARC / FIC in mouse) epithelial cell, fibroblasts, activated monocytes CCR1
CCR2
CCR3
Duffy antigen-related receptor for chemokines (DARC) (decoy)
CCL8 / MCP-2 / HC14 fibroblasts, activated monocytes CCR1
CCR2
CCR3
CD195 / CCR5 / BLR-1
CCL9 (MRP-2 / Scya9 / CCF18 / MIP-1gin mouse) APCs ?
CCL10 / MIP-1g
?
CCL11 / eotaxin / eotaxin-1 (catabolysed by CD26 / DPPIV) epithelial cell (including pneumocytes and endothelial cell), alveolar macrophage, smooth muscle cell, fibroblast, eosinophils, lymphocyte, cardiomyocytes CCR2 (both agonist and antagonist) 
CCR3
CD195 / CCR5 / BLR-1
CCL12 (MCP-5 in mouse)
CCR2
CCL13 / MCP-4 / CKb-10 / NCC-1 epithelial cell (including pneumocytes, enterocytes and activated endothelial cells) CCR1
CCR2
CCR3
CD195 / CCR5 / BLR-1
CCL14a / HCC-1 / NCC-2
CCR1
CCR3
CD195 / CCR5 / BLR-1
CCL14b / HCC-3
CCR1
CCR3
CD195 / CCR5 / BLR-1
CCL15 / HCC-2 / leukotactin / Lkn-1 / MIP-1d / MIP-5 / NCC-3
CCR1
CCR3
CD195 / CCR5 / BLR-1
CCL16 / HCC-4 / SexCkine / LEC / NCC-4 (LCC-1 in mouse)
CCR1
CCR2
CD195 / CCR5 / BLR-1
CCR8
CCL17 / thymus and activation-regulated chemokine (TARC) / dendrokine bronchiolar epithelial cells, thymus, dendritic cells, activated T lymphocytes CCR4
CCL18 / PARC / DC-CK-1 / MIP-4 / SCYA18 / AMAC-1 dendritic cells in secondary lymphoid organs unknown
CCL19 / MIP-3b / EBV-induced gene 1 ligand chemokine (ELC) / exodus-3 / CKb-11 thymus, lymph nodes, appendix CCR7 / CDw197
CCL20 / MIP-3a / exodus-1 / LARC dendritic cells, fetal hepatocytes, activated T lymphocytes CCR6
CCL21/ 6Ckine / exodus-2 / secondary lymphoid tissue chemokine (SLC) / TCA-4 TECs, lymph nodes, appendix and spleen, lymphatic endothelial cells (LEC) CCR7 / CDw197
CXCR3 / CD183 (in mice but not in humans)
CCL22 / macrophage-derived chemokine (MDC) / STCP-1 (ABCD-1 in mouse) (catabolysed by CD26 / DPPIV) smooth muscle cell, dendritic cells, monocytes, alveolar macrophage, bronchiolar epithelium, thymus CCR4
CCL23 / CKb-8 / MPIF-1
CCR1 (?)
CCL24 / eotaxin-2 / MPIF-2
CCR3
CCR4 (?)
CCL25 / TECK dendritic cells, thymus, hepatocytes, small bowel CCR9
CCL26/ eotaxin-3
CCR3
CCL27 / CTACK / ALP / ILC (ESkine in mouse; the alternative spliced isoform PESKY lacks a signal peptide and is translocated to the nucleus acting as an intrakine; also ESkine has a NTS) keratinocytes CCR10
CCL28 / MEC mucosal epithelial cells (expecially salivary and mammary glands => in saliva and breast milk) CCR3
CCR10
d-chemokines : CXXXC or CX3C motif CX3CL1 / fractalkine / neurotactin / ABCD-3 activated endothelial cells CX3CR1
g-chemokines : C motif (the prefix "X" is used to avoid confusion between g-chemokines receptors and complement receptors !) XCL1 / lymphotactin (Lptn or Ltn) /  SCM-1a / ATAC NK cells, DN thymocytes, activated CD8+ lymphocytes, lymphatic endothelial cells (LEC) XCR1
XCL2 / SCM-1b
XCR2
pleiotrophin / heparin binding growth factor 8 / neurite growth-promoting factor 1 (NGPF1) 



midkine (MDK) / neurite growth-promoting factor (NGPF2)

esophageal carcinoma, astrocytes, 
message domain
endogenous opiates / opioid peptides / endorphins (sensu latu) / narcotics and related peptides (close physiological linkage between the stress axis and opioid system)
produced by...
receptor(s)
Tyr-Gly-Gly-Phe proopiomelanocortin (POMC) (239 amino acids) =>
  • g-melanocyte stimulating hormone (g-MSH)
  • g2-melanocyte stimulating hormone (g2-MSH)
    • g1-melanocyte stimulating hormone (g1-MSH) / desGly-g2-MSH
  • g3-melanocyte stimulating hormone (g3-MSH)
  • adrenocorticotropic hormone (ACTH) / corticotropin
    • a-melanocyte stimulating hormone (a-MSH)
    • corticotropin-like intermediate peptide (CLIP)
  • b-lipotropin (b-LPH) / adipokinin
    • g-lipotropin (g-LPH)
      • b-melanocyte stimulating hormone (b-MSH)
    • b-endorphin (b-END) (31 amino acids). b-endorphin peptides may be N-acetylated to inactivated forms, while C-terminal processing may alter or regulate physiological functions. 
Melanocortins is the name given to peptides which share the common His-Phe-Arg-Trp core (i.e. MSHs and ACTH).
long interneurons in : 
  • anterior hypophysis (=> ACTH : hormone but also retrograde portal flux to CNS)
  • corticotropic cells of intermediate hypophysis  (=> a-MSH)
  • arcuate nucleus neurons producing also CART (=> a-MSH) => anterior septum, paraventricular nucleus of the thalamus, parabranchial nucleus, periaqueductal grey (PAG)
  • nucleus tractus solitarius =>  limbic and brainstem areas and spinal cord
  • spinal cord
pancreatic islet cells 
syncytiotrophoblast
MC1R
MC2R / ACTHR
MC3R
MC4R
MC5R
m
d
k1
k2
s1
s2
  • proenkephalin A (256 amino acids) =>
    • Met-enkephalin (M-ENK) : Tyr-Gly-Gly-Phe-Met 
    • peptide F
    • peptide E
      • octapeptide : Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu
      • Leu-enkephalin (L-ENK) : Tyr-Gly-Gly-Phe-Leu

      • They are catabolyzed by leucine aminopeptidase (LAP), carboxypeptidase A (CPA) and dipeptidyl-dipeptidase (DAP) / enkephalinase. The Tyr moiety is important for activity and probably corresponds to the 3-hydroxyl group on morphine. C-terminal amidation of peptides can occur following the enzymatic cleavage and removal of basic amino acids. The activity of the enkephalin peptides can be enhanced by replacement of Gly2 with D-Ala which decreases the hydrolysis of enkephalins by enkephalinases between the Tyr and Gly amino acids. Met5-amides also are resistant to hydrolysis.
    • Met-enkephalin (M-ENK)
    • heptapeptide : Tyr-Gly-Gly-Phe-Met-Arg-Phe 
    CNS : short interneurons in  : 
    • globus pallidus
    • caudate nucleus
    • amygdala
    • hippocampus
    • locus ceruleus
    • hypothalamus
    • cerebellum
    • substantia nigra
    • thalamus
    • medulla oblungata
    • median eminence
    • cortex
    • laminae I and II of the spinal cord
    • spinal trigeminal nucleus
    • periaqueductal grey (PAG)
    PNS 
    • CSF
    • posterior hypophysis
    • celial ganglion
    • upper cervical ganglion
    • salivary glands
    • nerve plexuses and exocrine glands of the stomach and intestine
    • adrenal medulla
    • blood
    m
    d
    k1
    k2
    s1
    s2
    proenkephalin B / prodynorphin
    • neoendorphin
    • dynorphin A (17 amino acids) : Tyr-Gly-Gly-Phe-Leu-Arg-Ile8-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln
    • dynorphin B (13 amino acids)
  • short interneurons in 
    • posterior hypophysis
    • CNS :
      • hypothalamus => magnocellular nucleus
      • striatonigral bundle
      • mesencephalus
      • hippocampus
      • pons
      • bulb
      • spinal cord (=> dorsal horns, marginal zone, deep laminae)
      • cortex
      • cerebellum
  • GI tract
  • skeletal muscles
  • pancreas
  • heart
  • lungs
  • liver
  • kidneys
  • testes
  • ovaries
  • m
    d
    k1
    k2
    s1
    s2

  • proorphanin / pronociceptin (in Mus musculus)
    • nocistatin (110MPRVRSLFQEQEEPEPGMEEAGEMEQKQLQ127)
    • nociceptin / orphanin FQ (N/OFQ) (130FQFGGFTGARKSARKLANQ146)
    • orphanin-2 (149FSEFMRQYLVLSMQSSQ165)
    hippocampus 
    cortex 
    periaqueductal grey 
    median raphe 
    superficial dorsal horn 
    rostral ventromedial medulla (RVM) 
    numerous sensory sites
    m
    d
    k1
    k2
    s1
    s2
    ORL-1
    Tyr-Pro-Trp/Phe endomorphin 1 (Tyr-Pro-Trp-Phe-NH2)
    m
    endomorphin 2 (Tyr-Pro-Phe-Phe-NH2)
    m
    CELL MEMBRANE TRANSPORT SIGNAL TRANSDUCTION PATHWAYS (STPs) companies offering equipment and reagents for cell signaling assays : AnaSpec, Applied Biosystems, BD Biosciences (Pharmingen), Biaffin GmbH, Bio-Rad,
    Biotrend Chemikalien GmbH, BioVisioN AG, Cambrex, Chemicon, Cell Signaling Technology, CGI Pharmaceuticals, Cue BIOtech, DiscoveRx, EMD Biosciences, Exalpha Biologicals, GE Healthcare (formerly Amersham), Globozymes, Imgenex, Intrexon, Invitrogen, Jerini AG, Kinasource, Kinexus Bioinformatics, MBL International, Molecular Devices, New England Biolabs, Olympus, Pepscan Systems, PerkinElmer, Pierce Biotechnology, Phosphosolutions, Promega, Qiagen, Rockland Immunochemicals, Serologicals, Sigma-Aldrich, Stratagene, Stressgen, Systat, Upstate, USBiological

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