Phosphorylation of the Type‐II Regulatory Subunit of Cyclic‐AMP‐Dependent Protein Kinase by Glycogen Synthase Kinase 3 and Glycogen Synthase Kinase 5

FEBS Journal - Tập 127 Số 3 - Trang 473-481 - 1982
Brian A. Hemmings1, Alastair Aitken1, Philip Cohen1, Michael RYMOND2, Franz Hofmann2
1Department of Biochemistry, University of Dundee, Dundee, Great Britain, DD1 4HN
2Pharmakologisches Institut der Ruprecht‐Karl‐Universität Heidelberg, Im Neuenheimer Feld 366, D‐6900 Heidelberg 1, Federal Republic of Germany

Tóm tắt

The regulatory (RII) subunit of type‐II cyclic‐AMP‐dependent protein kinase from bovine heart is phosphorylated at a significant rate in vitro by glycogen synthase kinase 3 and glycogen synthase 5, but not by glycogen synthase kinase 4 or phosphorylase kinase. The regulatory (RI) subunit of type‐I cyclic‐AMP‐dependent protein kinase from rabbit skeletal muscle is not phosphorylated by any of these four protein kinases.Glycogen synthase kinase 3 phosphorylates two serine residues on the RII subunit located 44 and 47 amino acids from the N terminus of the polypeptide chain. Glycogen synthase kinase 5 phosphorylates serine‐74 and serine‐76. These sites are distinct from the residue phosphorylated by the catalytic subunit of cyclic‐AMP‐dependent protein kinase (serine‐95).The RII subunit, as normally isolated, contains 1.5–1.8 mol alkali‐labile phosphate per subunit. At least 80% of this phosphate (∼ 1.3 mol/subunit) is located in the thermolytic peptide containing serine‐74 and serine‐76, demonstrating that phosphorylation of the RII subunit by glycogen synthase kinase 5 occurs in vivo. Only small amounts of phosphate (∼ 0.1 mol/subunit) are associated with the thermolytic peptides containing serine‐44/serine‐47 and serine‐95.The phosphorylation sites on the RII subunit are organised in a strikingly similar manner to those of glycogen synthase, the amino acid sequences in the immediate vicinity of the phosphorylation sites showing a particular resemblance. These include the presence of a number of proline residues near the sites phosphorylated by glycogen synthase kinase 3, five consecutive acidic residues C‐terminal to the sites phosphorylated by glycogen synthase kinase 5, and two adjacent arginine residues just N‐terminal to the sites phosphorylated by the catalytic subunit of cyclic‐AMP‐dependent protein kinase.Glycogen synthase kinase 5 is very similar or identical to the enzyme that has been variously termed casein kinase TS, casein kinase 2, casein kinase G, casein kinase N‐II or troponin‐T kinase. The biological role of this enzyme is reviewed.

Từ khóa


Tài liệu tham khảo

Nimmo H. G., 1977, Adv. Cyclic Nucleotide Res., 8, 145

Carlson G. M., 1979, Adv. Enzymol., 49, 42

Erlichman J., 1980, J. Biol. Chem., 255, 8179, 10.1016/S0021-9258(19)70627-9

10.1016/S0021-9258(19)42419-8

Huang T. S., 1979, Miami Winter Symp., 16, 449

10.1073/pnas.79.8.2544

10.1111/j.1432-1033.1982.tb06696.x

Dils W. C., 1975, Biochem. Biophys. Res. Commun., 62, 70, 10.1016/S0006-291X(75)80406-2

10.1016/0076-6879(74)38046-9

10.1111/j.1432-1033.1981.tb05628.x

Nimmo H. G., 1976, Eur. J. Biochem., 65, 21, 10.1111/j.1432-1033.1976.tb10761.x

10.1111/j.1432-1033.1978.tb12334.x

10.1111/j.1432-1033.1973.tb02721.x

10.1111/j.1432-1033.1982.tb05902.x

10.1016/S0021-9258(19)86069-6

10.1111/j.1432-1033.1981.tb05252.x

10.1111/j.1432-1033.1980.tb06059.x

10.1016/S0021-9258(19)45755-4

10.1016/S0021-9258(19)52451-6

10.1016/0003-2697(69)90172-9

10.1111/j.1432-1033.1975.tb03910.x

Parker P. J., 1982, Eur. J. Biochem., 124, 41, 10.1111/j.1432-1033.1982.tb05904.x

10.1111/j.1432-1033.1981.tb05160.x

10.1111/j.1432-1033.1980.tb06060.x

10.1016/0022-2836(70)90023-9

10.1016/S0021-9258(19)69637-7

10.1038/227680a0

10.1016/S0021-9258(19)85509-6

10.1016/S0021-9258(19)86801-1

10.1016/0014-5793(80)80865-9

10.1016/S0021-9258(18)43522-3

10.1111/j.1432-1033.1982.tb05903.x

10.1016/0014-5793(77)80084-7

10.1016/S0021-9258(17)37871-7

10.1210/endo-106-3-750

10.1016/S0021-9258(17)39899-X

10.1042/bj1910851

10.1016/S0006-291X(81)80117-9

Pearlston J. R., 1976, Proc. Natl Acad. Sci. USA, 73, 1902, 10.1073/pnas.73.6.1902

10.1016/0006-291X(79)91654-1

10.1111/j.1432-1033.1979.tb12918.x

Mercier J. C., 1971, Eur. J. Biochem., 25, 41, 10.1111/j.1432-1033.1971.tb01590.x

DePaoli‐Roach A. A., 1981, J. Biol. Chem., 256, 8955, 10.1016/S0021-9258(19)52492-9

10.1042/bj1410733

DePaoli A. A., 1981, J. Biol. Chem., 256, 8871, 10.1016/S0021-9258(19)52475-9

10.1016/S0021-9258(19)68504-2

Reference deleted.

10.1111/j.1432-1033.1981.tb05178.x

Thông tin
Thông tin xuất bản

FEBS Journal

Tập 127 Số 3

473-481

Thông tin tác giả