Biophysical interaction between phospholamban and protein phosphatase 1 regulatory subunit GM.
Regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. This process is reversed by a sarcoplasmic reticulum (SR)-associated type 1 protein phosphatase (PP1) composed of a catalytic subunit PP1C and a regulatory subunit GM. Human GM and PLB have been produced in an in vitro transcription/translation system and used for co-immunoprecipitation and biosensor experiments. The detected interaction between the two partners suggests that cardiac PPI is targeted to PLB via GM and we believe that this process occurs with the identified transmembrane domains of the two proteins. Thus, the interaction between PLB and GM may represent a specific way to modulate the SR function in human cardiac muscle.
Berrebi-Bertrand
I
I
SmithKline Beecham Laboratoires Pharmaceutiques, Saint-Grégoire, France. isabelle_bertrand@sbphrd.com
Souchet
M
M
Camelin
J C
JC
Laville
M P
MP
Calmels
T
T
Bril
A
A
D000595:Amino Acid Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011487:Protein Conformation; D054645:Protein Phosphatase 1; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D008565:Membrane Proteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D000099211:Phospholamban; C114205:PPP1R3A protein, human