Many low-molecular weight factors secreted by cells including fibroblasts,
macrophages and endothelial cells, in response to a variety of stimuli
such as growth factors, interferons, viral transformation and bacterial
products, are structurally related [1,2,3,E1]. Most members of this family of
proteins seem to have mitogenic, chemotactic or inflammatory activities. These
small cytokines are also called intercrines or chemokines. They are cationic
proteins of 70 to 100 amino acid residues that share four conserved cysteine
residues involved in two disulfide bonds, as shown in the following schematic
'C': conserved cysteine involved in a disulfide bond.
These proteins can be sorted into two groups based on the spacing of the two
amino-terminal cysteines. In the first group, the two cysteines are separated
by a single residue (C-x-C), while in the second group, they are adjacent
The 'C-x-C' group is currently known to consist of the following proteins:
- Platelet factor 4 (PF4), a protein released from platelet α-granules as
a complex with a proteoglycan molecule. PF4 neutralizes the anticoagulant
effect of heparin because it binds more strongly to heparin than to the
chondroitin-4-sulfate chains of the carrier molecule. PF4 is chemotactic
for neutrophils and monocytes.
- Platelet basic protein (PBP), which is the precursor of two active peptides:
connective-tissue activating peptide III (CTAP III) (also known as low-
affinity platelet factor IV (LA-PF4)) and β-thromboglobulin. CTAP-III is
a growth factor that stimulates a variety of specific metabolic and
- Interleukin-8 (IL-8), a monokine which is released from monocytes by an
inflammatory response and which is selectively chemotactic for neutrophils.
IL-8 is also known as Monocyte-Derived Neutrophil Chemotactic Factor
(MDNCF), or as Neutrophil Activating Protein 1 (NAP-1).
- Melanoma growth stimulatory activity protein (MGSA), a growth factor with
potent mitogenic activity. MGSA is also known as Neutrophil Activating
Protein 3 (NAP-3) or as 'gro', as KC or N51 in mouse and as CICN in rat.
- Macrophage inflammatory protein 2 (MIP-2), an extremely potent chemotactic
agent for polymorphonuclear leukocytes.
- Mouse Mig (m119), a γ-interferon induced protein that may be a cytokine
affecting the growth, movement or activation state of cells that
participate in immune and inflammatory response.
- Chicken 9E3 (or pCEF-4), a protein expressed constitutively in Rous Sarcoma
virus (RSV) infected cells and which may be an autocrine factor that
promotes the growth of fibroblasts.
- Pig alveolar macrophage chemotactic factors I and I (AMCF-I and -II).
- Pre-B cell growth stimulating factor (PBSF) (stromal cell-derived factor 1)
- IP10, a γ-interferon induced protein which is chemotactic for monocytes
and T lymphocytes.
The 'C-C' group is currently known to consist of the following proteins:
- Monocyte chemotactic protein 1 (MCP-1) [Also known as monocyte chemotactic
and activating factor (MCAF); JE].
- Monocyte chemotactic protein 2 (MCP-2).
- Monocyte chemotactic protein 3 (MCP-3) [Also known as MARC; FIC].
- Monocyte chemotactic protein 4 (MCP-4) [Also known as NCC-1].
- Macrophage inflammatory protein 1 α (MIP-1-α) [Also known as SIS-
α; TY-5; L2G25B; PAT 464.1; GOS19-1].
- Macrophage inflammatory protein 1 β (MIP-1-β) [Also known as SIS-
γ; H400; ACT-2; PAT 744].
- Macrophage inflammatory protein 1 γ (MIP-1-γ) [Also known as
macrophage inflammatory protein-related protein-2 (MRP2)].
- Macrophage inflammatory protein 3 α (MIP-3-α) [Also known as Liver
and Activation-Regulated Chemokine (LARC)].
- Macrophage inflammatory protein 3 β (MIP-3-β) [Also known as EBI1-
Ligand Chemokine (ELC)].
- Macrophage inflammatory protein 4 (MIP-4) [Also known as Pulmonary and
Activation-Regulated Chemokine (PARC)].
- Macrophage inflammatory protein 5 (MIP-5) [Also known as HCC-2; NCC-3].
- LD78 β (also known as PAT 464.2 or GOS19-2).
- RANTES [Also known as SIS-delta].
- SIS-epsilon (p500).
- Thymus and activation-regulated chemokine (TARC).
- Eotaxin [Also known as eosinophil chemotactic protein].
- I-309 [Also known as TCA3].
- Human protein HCC-1/NCC-2.
- Human protein HCC-3.
- Mouse protein C10.
For each of the two groups of proteins, we have developed a signature pattern
spanning the region that includes the four conserved cysteines.
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