Cytokines & Cells Online Pathfinder Encyclopaedia
|
Horst Ibelgaufts' COPE:
Cytokines & Cells Online Pathfinder Encyclopaedia |
 |
 |
 |
 |
 |
 |
|
| COPE Homepage | Bottom of page | Previous entry: EMAP-1 |
Next entry: Embryo-associated immunosuppressor factor |
Random entry: Small inducible cytokine A12 |
[Endothelial-monocyte activating polypeptide-2] This factor (approximately 22 kDa) is secreted into the conditioned medium of murine methylcholanthrene induced meth A fibrosarcoma cells (Kao et al, 1992, 1994) together with another unrelated factor, EMAP-1.
The human cDNA encodes a protein of 312 amino acids. Human and mouse EMAP-2 amino acid sequences share 86 % identity (Kao et al, 1994). The new designation for EMAP-2 is SCYE1 [small inducible cytokine subfamily E member 1] (see also: SCY family of cytokines).
EMAP-2 is synthesised as a 34 kDa precursor and cleaved enzymatically to produce a biologically active 22 kDa mature polypeptide. Quevillon et al (1997) have observed that the p43 subunit invariably associated with 9 aminoacyl-tRNA synthetase complexes is most likely the precursor of EMAP-2. P43 itself has been shown to function as a cytokine.
Shalak et al (2001) have shown that the EMAP-2 domain of p43 is released readily from the complex after in vitro digestion with caspase-7. The RNA binding capacity of p43 is lost upon the release of the EMAP-2 domain, suggesting that after onset of apoptosis, the first consequence of the cleavage of p43 is to limit the availability of tRNA for aminoacyl-tRNA synthetases associated within the complex and to cause translation arrest. Ko et al (2001) have shown that p43 itself is secreted from intact mammalian cells and suggest that p43 itself has activities of cytokines. They demonstrate that p43 activats MAPKs and NF-kappa-B, and that it induces expression of cytokines and chemokines such as TNF, IL8, MCP-1, MIP-1-alpha, MIP-1-beta, MIP-2-alpha, IL1-beta, and RANTES. The authors find high level of p43 in the foam cells of atherosclerotic lesions and suggest that p43 may mediate atherosclerosis development and other diseases associated with inflammation. A cytokine resembling EMAP-2 is contained also within the coding sequence of Tyrosyl-tRNA synthetase, from which it is split following release of the enzyme from cells undergoing apoptosis.
The N-terminal region of EMAP-2 defines a biologically active locus of the molecule. A synthetic peptide comprising 15 residues from the N-terminal region (residues 6-20) has been shown to induce directional migration of mononuclear phagocytes and polymorphonuclear leukocytes (Kao et al, 1994).
EMAP-2 has the ability to induce tissue factor procoagulant activity in endothelial cells (Kao et al, 1994). It induces migration of monocytes and is also chemotactic for granulocytes (see also: Chemotaxis). Injection of the polypeptide into mouse footpads elicits an inflammatory response with tissue swelling and infiltration of polymorphonuclear leukocytes (Kao et al, 1994).
EMAP-2 has been shown to be present in autoimmune lesions and may be a factor regulating chemoattraction of monocytes, cell activation of endothelial cells, and reactivity of microglial cells in autoimmune inflammation of the central nervous system (Schluesener et al, 1997).
EMAP-2 inhibits proliferation of endothelial cells and can induce cell death by apoptosis in endothelial cells (Berger et al, 2000). Schwarz et al (1999) have shown that EMAP-2 is a potent antitumor cytokine that suppresses primary and metastatic tumor growth and induces cell death by apoptosis in growing endothelial cells.
EMAP-2 has been shown to sensitize initially resistant murine and human tumors to regression induced by TNF (Marvin et al, 1996). Constitutive overexpression of EMAP-2 in a TNF-resistant human melanoma line by retroviral mediated transfer of EMAP-2 cDNA renders the tumor sensitive to the effects of systemic TNF in vivo, but not in vitro (Wu et al, 1999; Gnant et al, 1999). Tumour sensitization most likely is due to the upregulation of TNF receptors in endothelial cells (Berger et al, 2000)
Zheng et al (2001) have shown that systemic and topical administration of EMAP-2 in herpetic stromal keratitis markedly diminishes levels of virus induced angiogenesis and significantly reduces the severity of lesions by causing apoptosis in vascular endothelial cells. Yamamoto et al (2000) have suggested that EMAP-2 expression in glioblastoma might predict the clinical response to TNF therapy and potentially identify patients with cytokine-responsive tumors.
For other entries pertaining to cell death mechanisms see also the Apoptosis Dictionary section of this encyclopedia. See also: Angiogenesis Dictionary section of this encyclopedia for other entries directly bearing on factors and processes involved in the generation of new blood vessels.
LAST MODIFIED: January 2002
See REFERENCES for entry EMAP-2
| COPE Homepage | Top of Page |
| SUPPORT COPE | Intro | Subdictionaries | New Entries | Contribute data | COPE Credentials |
| # | A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z |
|
|
 |
 |
 |
 |
 |
 |
 |
supports the COPE bioinformatics project with an unrestricted educational grant |
Created, developed, and maintained by Prof Dr H Ibelgaufts
|
| Access to COPE is free only for academic institutions and non-profit organizations. OTHER USERS: must contact COPE and pay a site licence fee. Non-payment of the site licence fee is a serious breach of COPE's binding Usage Agreement. If you do not wish to be bound by this agreement, do not use COPE |
| COPE is not in the public domain! The commercial use of COPE contents is not allowed. Download of complete offline-readable copies and the use of automatic extraction methods are prohibited! Usage Agreement, Disclaimer, Copyright Notice | All rights reserved by H Ibelgaufts | Privacy Statement U L T R A P O S S E N E M O O B L I G A T U R |
