A novel plasma membrane Ca2+-pump inhibitor: caloxin 1A1

Pande, Jyoti; Mallhi, Kanwaldeep; Grover, Ashok K.

doi:10.1016/j.ejphar.2004.11.057

Cited by 25 publications

(21 citation statements)

References 12 publications

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“…Whereas a 12-amino acid random linear peptide library was used for other caloxins, caloxin 1a1 was selected from a cyclic library [89]. The cyclic library encoded seven amino acid random peptides, flanked by two cysteine residues, which formed an internal cross bridge.…”

Section: Series a Caloxinsmentioning

confidence: 99%

Caloxins: a novel class of selective plasma membrane Ca2+ pump inhibitors obtained using biotechnology

Szewczyk

Pande

Grover

2007

Pflugers Arch - Eur J Physiol

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Plasma membrane Ca2+ pumps (PMCA) extrude cellular Ca2+ with a high affinity and hence play a major role in Ca2+ homeostasis and signaling. Caloxins (selective extracellular PMCA inhibitors) would aid in elucidating the physiology of PMCA. PMCA proteins have five extracellular domains (exdoms). Our hypotheses are: 1) peptides that bind selectively to each exdom can be invented by screening a random peptide library, and 2) a peptide can modulate PMCA activity by binding to one of the exdoms. The first caloxin 2a1, selected for binding exdom 2 was selective for PMCA (Ki=529 microM). It has been used to examine the physiological role of PMCA. PMCA isoforms are encoded by four genes. PMCA isoform expression differs in various cell types, with PMCA1 and 4 being the most widely distributed. There are differences between PMCA1-4 exdom 1 sequences, which may be exploited for inventing isoform selective caloxins. Using exdom 1 of PMCA4 as a target, modified screening procedures and mutagenesis led to the high-affinity caloxin 1c2 (Ki=2.3 microM for PMCA4). It is selective for PMCA4 over PMCA1, 2, or 3. We hope that caloxins can be used to discern the roles of individual PMCA isoforms in Ca2+ homeostasis and signaling. Caloxins may also become clinically useful in cardiovascular diseases, neurological disorders, retinopathy, cancer, and contraception.

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Section: Series a Caloxinsmentioning

confidence: 99%

Caloxins: a novel class of selective plasma membrane Ca2+ pump inhibitors obtained using biotechnology

Szewczyk

Pande

Grover

2007

Pflugers Arch - Eur J Physiol

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“…Так, концентрація фосфатидилсерину та подібних до нього кис-лих фосфоліпідів у ПМ незмінна для кожного окремого типу клітин, натомість концентрація фосфатидилінозитолу та його фосфорилованих продуктів (РІР 1,2 ) у мембрані змінюється під впливом регуляторних систем клітини, що ро-бить їх імовірнішими модуляторами активності Са 2+ -помпи ПМ [35]. Загалом, поміж перелічених сполук фосфатидилінозитол-4,5-бісфосфат є найефективнішим стимулятором помпи [8,30]. Таким чином, РІР 2 важливий для збереження активності Са 2+ -помпи ПМ у клітинах у стані спокою, коли концентрація вільного Са 2+ є низь-кою та стимуляція кальмудуліном є мінімальною [8,30,66].…”

Section: ліпідне оточенняunclassified

“…Загалом, поміж перелічених сполук фосфатидилінозитол-4,5-бісфосфат є найефективнішим стимулятором помпи [8,30]. Таким чином, РІР 2 важливий для збереження активності Са 2+ -помпи ПМ у клітинах у стані спокою, коли концентрація вільного Са 2+ є низь-кою та стимуляція кальмудуліном є мінімальною [8,30,66]. Варто зазначити, що концентрація РІР 1,2 залежить від Са 2+ -споріднених сигналь-них процесів, тому можливий зворотний цикл регуляції Са 2+ -помпи ПМ [48].…”

Section: ліпідне оточенняunclassified

Mg(2+),ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

Veklich¹

2015

Ukr.Biochem.J.

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“…The inhibition is noncompetitive with respect to the substrates and calmodulin [157]. Caloxin1A1 inhibits PMCA by binding to the first extracellular domain [135] while caloxin1B1 is isoform selective with a higher affinity for PMCA4 than PMCA1 [158]. The effect of spermine, particularly, is highly specific; inhibition resulting from the decrease in the rate of dissociation of Ca 2+ from the phosphorylated ATPase (Ca 2 E 1 P → E 2 P) [142].…”

Section: +mentioning

confidence: 99%

“…Caloxin 2A1 does not affect the activities of Mg 2+ -ATPase or Na + , K + ATPase in the erythrocyte ghosts, SERCA1 Ca 2+ , Mg 2+ -ATPase in fast twitch skeletal muscle. Caloxin 3A1, based on PED3, inhibits the PMCA pump but not the sarcoplasmic reticulum Ca 2+ pump [135].…”

Section: Regulation Ofmentioning

confidence: 99%

Endogenous modulators in the regulation of ion transporting enzymes: structure, function, interactions, recent advancements and future perspectives

Sen¹

2011

ABC

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A prerequisite for life is the ability to uphold electrochemical imbalance across biomembranes. Ion transporting enzymes, known as specific pumps, are responsible for the transport of various ions across cell membranes to sustain the same. In all eukaryotes, the plasma membrane potential and secondary transport systems are maintained by the activity of P-type ion transporting enzymes, commonly known as ATPase membrane pumps. Malfunction of pumps leads to various cell disorders and subsequently diseases like cardiac problems, renal malfunctionings, diabetes, cataract, even cancer. Activities/functions of these pumps are regulated either by exogenous agents or by endogenous substances like proteins, peptides, hormones, etc., which are collectively known as modulators. Some of these endogenous modulators may be useful for developing drugs depending on the nature of regulation. For more than last two decades, researchers across the globe are exploring the mechanism of action of different endogenous modulators on these ion transporting enzymes with the aim of developing target-specific drugs. In this review, we have discussed recent advances in our understanding of ATPase pumps, e.g., Ca 2+ -, Na

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A novel plasma membrane Ca2+-pump inhibitor: caloxin 1A1

Cited by 25 publications

References 12 publications

Caloxins: a novel class of selective plasma membrane Ca2+ pump inhibitors obtained using biotechnology

Caloxins: a novel class of selective plasma membrane Ca2+ pump inhibitors obtained using biotechnology

Mg(2+),ATP-dependent plasma membrane calcium pump of smooth muscle cells. ІІ. Regulation of activity

Endogenous modulators in the regulation of ion transporting enzymes: structure, function, interactions, recent advancements and future perspectives

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