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Cocaine- and Amphetamine Related Transcript (CART)
Cocaine- and Amphetamine Related Transcript (CART) was initially identified using PCR differential display as mRNA whose levels in the brain was specifically induced by psychomotor stimulants such as cocaine and amphetamine (1). CART encodes a secretory single chain polypeptide of 129 AA or 116 AA protein due to the usage of alternate splicing and processing. The first 27 AA represents the hydrophobic core indicative of signal peptide. The CART protein also has several basic amino acids near the 54-66 residues with a potential to form multiple proteolytic forms. CART mRNA was specially enriched in the hypothalamus. Low level expression of CART was also found in the eye, adrenal, and pituitary, while no signal was detected in other rat issues. Thus basal expression of CART is limited to neuroendocrine tissues. In the striatum, CART expression was induced 4-5 fold by cocaine and amphetamine. CART is highly conserved between human and mouse (95% amino acid homology); CART gene was localized to human chromosome 5 (2). Several key signaling molecules are found in the hypothalamus that controls the ingestive behavior in the mammals. Most recently, CART has been found to control satiety modulating the actions of two key regulators of food intake, leptin and NPY. Starvation decreases CART levels in the arcuate nucleus (3). Obese animals have virtually no CART. Peripheral administration of leptin in obese animals induces CART. Intracereberoventricular injection of recombinant CART inhibits both normal and starvation-induce feeding, and completely inhibits NPY-induce feeding. Immunoneutralization of CART by administration of anti-CART resulted into higher food intake suggesting that CART is an endogenous regulator of food intake. When CART cDNA was expressed in yeast, multiple post-translationally processed forms were observed (3). Indeed CART 55-102 (numbers corresponds to the predicted signal-peptide-cleavage site in the long form of CART) was physiologically active in inhibiting feeding in normal rats (3). It has been suggested that a proportional reduction in NPY and an increase in CART control leptin-mediated suppression of food intake. Therefore CART represents another therapeutic target to control food intake and obesity. ADI has produced highly specific antibodies to CART. Physiologically active CART (55-102) and biotinylated CART are available to further investigate CART action at the cellular and molecular levels.
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mCART. MESSRLRLLPLLGAAILLLLPLLGARAQEDAELQPRALDIYSAVDDASHEKELPRRQLRA
rCART. MESSRLRLLPVLGAALLLLLPLLGAGAQEDAELQPRALDIYSAVDDASHEKELPRRQLRA
hCART. MESSRVRLLPLLGAALLLMLPLLGTRAQEDAELQPRALDIYSAVDDASHEKEL-------
*****:****:****:**:*****: ***************************
mCART. PGAMLQIEALQEVLKKLKSKR(IPIYEKKYGQVPMCDAGEQCAVRKGARIGKLCDCPRGTS
rCART. PGAVLQIEALQEVLKKLKSKR(IPIYEKKYGQVPMCDAGEQCAVRKGARIGKLCDCPRGTS
hCART. ------IEALQEVLKKLKSKR(VPIYEKKYGQVPMCDAGEQCAVRKGARIGKLCDCPRGTS
*************** :**************************************
mCART. CNSFLLKCL)
rCART. CNSFLLKCL)
hCART. CNSFLLKCL)
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Mouse (m), Rat (r) and human (h) CART (residues in parenthesis represents 55-102 CART).
M/R
CART,
55-102 AA, Cat # CART11-P, 1 mg; (100 ug; Cat # CART13-P) | ||||||||||||||||||||||||||||||||||||
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