Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)
Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interactions between the cyclic nucleotide and Ca2+ second messenger systems. Currently, three genes encode PDE1, and alternate splicing of these genes gives rise to functionally di...
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| description | Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interactions between the cyclic nucleotide and Ca2+ second messenger systems. Currently, three genes encode PDE1, and alternate splicing of these genes gives rise to functionally different isozymes which exhibit distinct catalytic and regulatory properties. Some isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. These isozymes also differ in their mechanism of regulation by phosphorylation. Analysis of various regulatory reactions involving Ca2+ and cyclic adenosine monophosphate (cAMP) has revealed the importance of the time dependence of these reactions during cell activation; however, no measurement is available for the time of occurrence of specific regulatory reactions. cAMP-signalling systems provide a pivotal centre for achieving crosstalk regulation by various signalling pathways. It has been proposed that polypeptide sequences enriched in proline (P), glutamate (E), serine (S) and threonine (T), known as PEST motifs, serve as putative intramolecular signals for rapid proteolytic degradation by calpains. Calpains are Ca(2+)-dependent cysteine proteases that regulate various enzymes, transcription factors and structural proteins through limited proteolysis. Isozyme PDE1A2 has a PEST motif and acts as a substrate for m-calpain. In this paper, we have described PDE1A2 regulation by calpains and its physiological implications. cAMP is an important component of the signal transduction pathway and plays an integral role in various physiological processes such as gene transcription, various neuronal functions, cardiac muscle contraction, vascular relaxation, cell proliferation and a host of other functions. It is important to identify the cellular processes where PDE isoform(s) and cAMP response are altered. This will lead to better understanding of the pathology of disease states and development of novel therapeutics. The different PDE1 isozymes, although similar in kinetic properties, can be distinguished by various pharmacological agents. Our recent understanding of the role of PDE1 inhibitors such as ginseng, dihydropy-ridine antagonists and antiparkinsonian agents are described in this review. The exact function of PDE1 isozymes in various pathophysiological processes is not clear because most of the studies have been carried out in vitro; therefore, it is essential tha |
| doi_str_mv | 10.1007/s000180050364 |
| format | Article |
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Currently, three genes encode PDE1, and alternate splicing of these genes gives rise to functionally different isozymes which exhibit distinct catalytic and regulatory properties. Some isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. These isozymes also differ in their mechanism of regulation by phosphorylation. Analysis of various regulatory reactions involving Ca2+ and cyclic adenosine monophosphate (cAMP) has revealed the importance of the time dependence of these reactions during cell activation; however, no measurement is available for the time of occurrence of specific regulatory reactions. cAMP-signalling systems provide a pivotal centre for achieving crosstalk regulation by various signalling pathways. It has been proposed that polypeptide sequences enriched in proline (P), glutamate (E), serine (S) and threonine (T), known as PEST motifs, serve as putative intramolecular signals for rapid proteolytic degradation by calpains. Calpains are Ca(2+)-dependent cysteine proteases that regulate various enzymes, transcription factors and structural proteins through limited proteolysis. Isozyme PDE1A2 has a PEST motif and acts as a substrate for m-calpain. In this paper, we have described PDE1A2 regulation by calpains and its physiological implications. cAMP is an important component of the signal transduction pathway and plays an integral role in various physiological processes such as gene transcription, various neuronal functions, cardiac muscle contraction, vascular relaxation, cell proliferation and a host of other functions. It is important to identify the cellular processes where PDE isoform(s) and cAMP response are altered. This will lead to better understanding of the pathology of disease states and development of novel therapeutics. The different PDE1 isozymes, although similar in kinetic properties, can be distinguished by various pharmacological agents. Our recent understanding of the role of PDE1 inhibitors such as ginseng, dihydropy-ridine antagonists and antiparkinsonian agents are described in this review. The exact function of PDE1 isozymes in various pathophysiological processes is not clear because most of the studies have been carried out in vitro; therefore, it is essential that further research be directed to in vivo studies.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s000180050364</identifier><identifier>PMID: 10442095</identifier><language>eng</language><publisher>Switzerland: Springer Nature B.V</publisher><subject>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors ; 3',5'-Cyclic-AMP Phosphodiesterases - chemistry ; 3',5'-Cyclic-AMP Phosphodiesterases - genetics ; 3',5'-Cyclic-AMP Phosphodiesterases - physiology ; 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors ; 3',5'-Cyclic-GMP Phosphodiesterases - chemistry ; 3',5'-Cyclic-GMP Phosphodiesterases - genetics ; 3',5'-Cyclic-GMP Phosphodiesterases - physiology ; 3',5'-Cyclic-nucleotide phosphodiesterase ; Alternative splicing ; Animals ; Antagonists ; Brain - enzymology ; Calcium ; Calcium Signaling - physiology ; Calcium-binding protein ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases - physiology ; Calmodulin ; Calmodulin - physiology ; Calpain ; Calpain - physiology ; Cardiac muscle ; Cattle ; Cell activation ; Cell proliferation ; Cyclic AMP ; Cyclic AMP - physiology ; Cyclic Nucleotide Phosphodiesterases, Type 1 ; Cyclic nucleotides ; Cysteine proteinase ; dihydropyridine ; Drug development ; Enzyme Activation ; Enzymes ; Ginseng ; Glutamic acid ; Humans ; Immunology ; Isoenzymes ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - chemistry ; Isoenzymes - genetics ; Isoenzymes - physiology ; Kinetics ; Male ; Muscle contraction ; Neoplasm Proteins - physiology ; Neoplasms - enzymology ; Nerve Tissue Proteins - physiology ; Organ Specificity ; Parkinson Disease - enzymology ; Pests ; Pharmacology ; Phosphoric Diester Hydrolases ; Phosphorylation ; Physiology ; Proline ; Protein Processing, Post-Translational ; Protein Structure, Tertiary ; Proteins ; Proteolysis ; Rats ; RNA Splicing ; Second Messenger Systems - physiology ; Second messengers ; Serine ; Signal transduction ; Structural proteins ; Threonine ; Transcription factors</subject><ispartof>Cellular and molecular life sciences : CMLS, 1999-07, Vol.55 (8-9), p.1164-1186</ispartof><rights>Birkhäuser Verlag Basel, 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-780b8bf275c8eaf93c25aa11e102a30ed81b0b63d0891e5478882b9dd8f317f53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146777/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146777/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10442095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kakkar, R</creatorcontrib><creatorcontrib>Raju, R V</creatorcontrib><creatorcontrib>Sharma, R K</creatorcontrib><title>Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)</title><title>Cellular and molecular life sciences : CMLS</title><addtitle>Cell Mol Life Sci</addtitle><description>Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interactions between the cyclic nucleotide and Ca2+ second messenger systems. Currently, three genes encode PDE1, and alternate splicing of these genes gives rise to functionally different isozymes which exhibit distinct catalytic and regulatory properties. Some isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. These isozymes also differ in their mechanism of regulation by phosphorylation. Analysis of various regulatory reactions involving Ca2+ and cyclic adenosine monophosphate (cAMP) has revealed the importance of the time dependence of these reactions during cell activation; however, no measurement is available for the time of occurrence of specific regulatory reactions. cAMP-signalling systems provide a pivotal centre for achieving crosstalk regulation by various signalling pathways. It has been proposed that polypeptide sequences enriched in proline (P), glutamate (E), serine (S) and threonine (T), known as PEST motifs, serve as putative intramolecular signals for rapid proteolytic degradation by calpains. Calpains are Ca(2+)-dependent cysteine proteases that regulate various enzymes, transcription factors and structural proteins through limited proteolysis. Isozyme PDE1A2 has a PEST motif and acts as a substrate for m-calpain. In this paper, we have described PDE1A2 regulation by calpains and its physiological implications. cAMP is an important component of the signal transduction pathway and plays an integral role in various physiological processes such as gene transcription, various neuronal functions, cardiac muscle contraction, vascular relaxation, cell proliferation and a host of other functions. It is important to identify the cellular processes where PDE isoform(s) and cAMP response are altered. This will lead to better understanding of the pathology of disease states and development of novel therapeutics. The different PDE1 isozymes, although similar in kinetic properties, can be distinguished by various pharmacological agents. Our recent understanding of the role of PDE1 inhibitors such as ginseng, dihydropy-ridine antagonists and antiparkinsonian agents are described in this review. The exact function of PDE1 isozymes in various pathophysiological processes is not clear because most of the studies have been carried out in vitro; therefore, it is essential that further research be directed to in vivo studies.</description><subject>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors</subject><subject>3',5'-Cyclic-AMP Phosphodiesterases - chemistry</subject><subject>3',5'-Cyclic-AMP Phosphodiesterases - genetics</subject><subject>3',5'-Cyclic-AMP Phosphodiesterases - physiology</subject><subject>3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors</subject><subject>3',5'-Cyclic-GMP Phosphodiesterases - chemistry</subject><subject>3',5'-Cyclic-GMP Phosphodiesterases - genetics</subject><subject>3',5'-Cyclic-GMP Phosphodiesterases - physiology</subject><subject>3',5'-Cyclic-nucleotide phosphodiesterase</subject><subject>Alternative splicing</subject><subject>Animals</subject><subject>Antagonists</subject><subject>Brain - enzymology</subject><subject>Calcium</subject><subject>Calcium Signaling - physiology</subject><subject>Calcium-binding protein</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - physiology</subject><subject>Calmodulin</subject><subject>Calmodulin - physiology</subject><subject>Calpain</subject><subject>Calpain - physiology</subject><subject>Cardiac muscle</subject><subject>Cattle</subject><subject>Cell activation</subject><subject>Cell proliferation</subject><subject>Cyclic AMP</subject><subject>Cyclic AMP - physiology</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 1</subject><subject>Cyclic nucleotides</subject><subject>Cysteine proteinase</subject><subject>dihydropyridine</subject><subject>Drug development</subject><subject>Enzyme Activation</subject><subject>Enzymes</subject><subject>Ginseng</subject><subject>Glutamic acid</subject><subject>Humans</subject><subject>Immunology</subject><subject>Isoenzymes</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - chemistry</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - physiology</subject><subject>Kinetics</subject><subject>Male</subject><subject>Muscle contraction</subject><subject>Neoplasm Proteins - physiology</subject><subject>Neoplasms - enzymology</subject><subject>Nerve Tissue Proteins - physiology</subject><subject>Organ Specificity</subject><subject>Parkinson Disease - enzymology</subject><subject>Pests</subject><subject>Pharmacology</subject><subject>Phosphoric Diester Hydrolases</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Proline</subject><subject>Protein Processing, Post-Translational</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Rats</subject><subject>RNA Splicing</subject><subject>Second Messenger Systems - physiology</subject><subject>Second messengers</subject><subject>Serine</subject><subject>Signal transduction</subject><subject>Structural proteins</subject><subject>Threonine</subject><subject>Transcription factors</subject><issn>1420-682X</issn><issn>1420-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1LxDAQxYMofh-9yuJB9FCdaZMmOS2yfoKgBwVvIU2mWuk2a7MV_O-N7CLqwcMwA_Pj8WYeY3sIJwggTyMAoAIQUJR8hW0izyHTIHF1OZcqf9pgWzG-JlCovFxnGwg8rbTYZOOJbafBD23TZZ5m1Hnq5iP34drGjbrBtRTmjafR7CXEVL6hOKfeRhod3Z9f4PEOW6ttG2l32bfZ4-XFw-Q6u727upmc3WaOcz7PpIJKVXUuhVNka124XFiLSAi5LYC8wgqqsvCgNJLgUimVV9p7VRcoa1Fss_FCdzZUU_Iuuexta2Z9M7X9hwm2Mb83XfNinsO7QUReSimTwuFSoQ9vQzrDTJvoqG1tR2GIptRacC50Ao_-BRFQJjSZTOjBH_Q1DH2XHmGU4mXBueYJyhaQ60OMPdXfrhHMV4bmV4aJ3_956g96EVrxCZXqldg</recordid><startdate>19990701</startdate><enddate>19990701</enddate><creator>Kakkar, R</creator><creator>Raju, R V</creator><creator>Sharma, R K</creator><general>Springer Nature B.V</general><general>Birkhäuser Verlag</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19990701</creationdate><title>Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)</title><author>Kakkar, R ; Raju, R V ; Sharma, R K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-780b8bf275c8eaf93c25aa11e102a30ed81b0b63d0891e5478882b9dd8f317f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors</topic><topic>3',5'-Cyclic-AMP Phosphodiesterases - chemistry</topic><topic>3',5'-Cyclic-AMP Phosphodiesterases - genetics</topic><topic>3',5'-Cyclic-AMP Phosphodiesterases - physiology</topic><topic>3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors</topic><topic>3',5'-Cyclic-GMP Phosphodiesterases - chemistry</topic><topic>3',5'-Cyclic-GMP Phosphodiesterases - genetics</topic><topic>3',5'-Cyclic-GMP Phosphodiesterases - physiology</topic><topic>3',5'-Cyclic-nucleotide phosphodiesterase</topic><topic>Alternative splicing</topic><topic>Animals</topic><topic>Antagonists</topic><topic>Brain - enzymology</topic><topic>Calcium</topic><topic>Calcium Signaling - physiology</topic><topic>Calcium-binding protein</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - physiology</topic><topic>Calmodulin</topic><topic>Calmodulin - physiology</topic><topic>Calpain</topic><topic>Calpain - physiology</topic><topic>Cardiac muscle</topic><topic>Cattle</topic><topic>Cell activation</topic><topic>Cell proliferation</topic><topic>Cyclic AMP</topic><topic>Cyclic AMP - physiology</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 1</topic><topic>Cyclic nucleotides</topic><topic>Cysteine proteinase</topic><topic>dihydropyridine</topic><topic>Drug development</topic><topic>Enzyme Activation</topic><topic>Enzymes</topic><topic>Ginseng</topic><topic>Glutamic acid</topic><topic>Humans</topic><topic>Immunology</topic><topic>Isoenzymes</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - chemistry</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - physiology</topic><topic>Kinetics</topic><topic>Male</topic><topic>Muscle contraction</topic><topic>Neoplasm Proteins - physiology</topic><topic>Neoplasms - enzymology</topic><topic>Nerve Tissue Proteins - physiology</topic><topic>Organ Specificity</topic><topic>Parkinson Disease - enzymology</topic><topic>Pests</topic><topic>Pharmacology</topic><topic>Phosphoric Diester Hydrolases</topic><topic>Phosphorylation</topic><topic>Physiology</topic><topic>Proline</topic><topic>Protein Processing, Post-Translational</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Proteolysis</topic><topic>Rats</topic><topic>RNA Splicing</topic><topic>Second Messenger Systems - physiology</topic><topic>Second messengers</topic><topic>Serine</topic><topic>Signal transduction</topic><topic>Structural proteins</topic><topic>Threonine</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kakkar, R</creatorcontrib><creatorcontrib>Raju, R V</creatorcontrib><creatorcontrib>Sharma, R K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cellular and molecular life sciences : CMLS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kakkar, R</au><au>Raju, R V</au><au>Sharma, R K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1)</atitle><jtitle>Cellular and molecular life sciences : CMLS</jtitle><addtitle>Cell Mol Life Sci</addtitle><date>1999-07-01</date><risdate>1999</risdate><volume>55</volume><issue>8-9</issue><spage>1164</spage><epage>1186</epage><pages>1164-1186</pages><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is one of the key enzymes involved in the complex interactions between the cyclic nucleotide and Ca2+ second messenger systems. Currently, three genes encode PDE1, and alternate splicing of these genes gives rise to functionally different isozymes which exhibit distinct catalytic and regulatory properties. Some isozymes have similar kinetic and immunological properties but are differentially regulated by Ca2+ and calmodulin. These isozymes also differ in their mechanism of regulation by phosphorylation. Analysis of various regulatory reactions involving Ca2+ and cyclic adenosine monophosphate (cAMP) has revealed the importance of the time dependence of these reactions during cell activation; however, no measurement is available for the time of occurrence of specific regulatory reactions. cAMP-signalling systems provide a pivotal centre for achieving crosstalk regulation by various signalling pathways. It has been proposed that polypeptide sequences enriched in proline (P), glutamate (E), serine (S) and threonine (T), known as PEST motifs, serve as putative intramolecular signals for rapid proteolytic degradation by calpains. Calpains are Ca(2+)-dependent cysteine proteases that regulate various enzymes, transcription factors and structural proteins through limited proteolysis. Isozyme PDE1A2 has a PEST motif and acts as a substrate for m-calpain. In this paper, we have described PDE1A2 regulation by calpains and its physiological implications. cAMP is an important component of the signal transduction pathway and plays an integral role in various physiological processes such as gene transcription, various neuronal functions, cardiac muscle contraction, vascular relaxation, cell proliferation and a host of other functions. It is important to identify the cellular processes where PDE isoform(s) and cAMP response are altered. This will lead to better understanding of the pathology of disease states and development of novel therapeutics. The different PDE1 isozymes, although similar in kinetic properties, can be distinguished by various pharmacological agents. Our recent understanding of the role of PDE1 inhibitors such as ginseng, dihydropy-ridine antagonists and antiparkinsonian agents are described in this review. The exact function of PDE1 isozymes in various pathophysiological processes is not clear because most of the studies have been carried out in vitro; therefore, it is essential that further research be directed to in vivo studies.</abstract><cop>Switzerland</cop><pub>Springer Nature B.V</pub><pmid>10442095</pmid><doi>10.1007/s000180050364</doi><tpages>23</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cellular and molecular life sciences : CMLS, 1999-07, Vol.55 (8-9), p.1164-1186 |
| issn | 1420-682X 1420-9071 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11146777 |
| source | MEDLINE; PubMed Central; SpringerLink Journals - AutoHoldings |
| subjects | 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors 3',5'-Cyclic-AMP Phosphodiesterases - chemistry 3',5'-Cyclic-AMP Phosphodiesterases - genetics 3',5'-Cyclic-AMP Phosphodiesterases - physiology 3',5'-Cyclic-GMP Phosphodiesterases - antagonists & inhibitors 3',5'-Cyclic-GMP Phosphodiesterases - chemistry 3',5'-Cyclic-GMP Phosphodiesterases - genetics 3',5'-Cyclic-GMP Phosphodiesterases - physiology 3',5'-Cyclic-nucleotide phosphodiesterase Alternative splicing Animals Antagonists Brain - enzymology Calcium Calcium Signaling - physiology Calcium-binding protein Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases - physiology Calmodulin Calmodulin - physiology Calpain Calpain - physiology Cardiac muscle Cattle Cell activation Cell proliferation Cyclic AMP Cyclic AMP - physiology Cyclic Nucleotide Phosphodiesterases, Type 1 Cyclic nucleotides Cysteine proteinase dihydropyridine Drug development Enzyme Activation Enzymes Ginseng Glutamic acid Humans Immunology Isoenzymes Isoenzymes - antagonists & inhibitors Isoenzymes - chemistry Isoenzymes - genetics Isoenzymes - physiology Kinetics Male Muscle contraction Neoplasm Proteins - physiology Neoplasms - enzymology Nerve Tissue Proteins - physiology Organ Specificity Parkinson Disease - enzymology Pests Pharmacology Phosphoric Diester Hydrolases Phosphorylation Physiology Proline Protein Processing, Post-Translational Protein Structure, Tertiary Proteins Proteolysis Rats RNA Splicing Second Messenger Systems - physiology Second messengers Serine Signal transduction Structural proteins Threonine Transcription factors |
| title | Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T23%3A02%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Calmodulin-dependent%20cyclic%20nucleotide%20phosphodiesterase%20(PDE1)&rft.jtitle=Cellular%20and%20molecular%20life%20sciences%20:%20CMLS&rft.au=Kakkar,%20R&rft.date=1999-07-01&rft.volume=55&rft.issue=8-9&rft.spage=1164&rft.epage=1186&rft.pages=1164-1186&rft.issn=1420-682X&rft.eissn=1420-9071&rft_id=info:doi/10.1007/s000180050364&rft_dat=%3Cproquest_pubme%3E69954459%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=884634494&rft_id=info:pmid/10442095&rfr_iscdi=true |