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Differential phosphorylation of Akt1 and Akt2 by protein kinase CK2 may account for isoform specific functions.

Girardi, Cristina; James, Peter LU ; Zanin, Sofia; Pinna, Lorenzo A and Ruzzene, Maria (2014) In Biochimica et Biophysica Acta 1843(9). p.1865-1874
Abstract
Akt (also known as PKB) is a survival kinase frequently up-regulated in cancer; three isoforms of Akt exist, and among them Akt1 and Akt2 are the most widely and highly expressed. They share the same structure and activation mechanism and have many overlapping functions; nevertheless isoform-specific roles and substrates have been reported, which are expected to rely on sequence diversities. In particular, a special role in differentiating Akt1 and Akt2 isoforms has been assigned to the linker region, a short segment between the PH and the catalytic domains. We have previously found that a residue in the linker region (Ser129) is directly phosphorylated by protein kinase CK2 in Akt1; the phosphorylation of the homologous residue in Akt2... (More)
Akt (also known as PKB) is a survival kinase frequently up-regulated in cancer; three isoforms of Akt exist, and among them Akt1 and Akt2 are the most widely and highly expressed. They share the same structure and activation mechanism and have many overlapping functions; nevertheless isoform-specific roles and substrates have been reported, which are expected to rely on sequence diversities. In particular, a special role in differentiating Akt1 and Akt2 isoforms has been assigned to the linker region, a short segment between the PH and the catalytic domains. We have previously found that a residue in the linker region (Ser129) is directly phosphorylated by protein kinase CK2 in Akt1; the phosphorylation of the homologous residue in Akt2 (Ser131) has never been analyzed. Here we show that Akt2, endogenously or ectopically expressed in different cell lines, is not phosphorylated on Ser131 by CK2, while in vitro recombinant Akt2 is a CK2 substrate. These data support the hypothesis that in vivo a steric hindrance occurs which prevents the access to the CK2 site. Additionally, we have found that Ser129 phosphorylation is involved in the recognition of the Akt1-specific substrate palladin; this observation provides an explanation of why Akt2, lacking Ser131 phosphorylation in the linker region, has a low efficiency in targeting palladin. CK2-dependent phosphorylation is therefore a crucial event which, discriminating between Akt1 and Akt2, can account for different substrate specificity, and, more in general, for fine tuning of Akt activity in the control of isoform-dependent processes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochimica et Biophysica Acta
volume
1843
issue
9
pages
1865 - 1874
publisher
Elsevier
external identifiers
  • pmid:24769357
  • wos:000339535300008
  • scopus:84902491248
ISSN
0006-3002
DOI
10.1016/j.bbamcr.2014.04.020
language
English
LU publication?
yes
id
000c92b3-6e64-41bd-a8e5-4c6d73b6c4e9 (old id 4429398)
date added to LUP
2014-05-06 10:42:21
date last changed
2017-10-29 03:54:04
@article{000c92b3-6e64-41bd-a8e5-4c6d73b6c4e9,
  abstract     = {Akt (also known as PKB) is a survival kinase frequently up-regulated in cancer; three isoforms of Akt exist, and among them Akt1 and Akt2 are the most widely and highly expressed. They share the same structure and activation mechanism and have many overlapping functions; nevertheless isoform-specific roles and substrates have been reported, which are expected to rely on sequence diversities. In particular, a special role in differentiating Akt1 and Akt2 isoforms has been assigned to the linker region, a short segment between the PH and the catalytic domains. We have previously found that a residue in the linker region (Ser129) is directly phosphorylated by protein kinase CK2 in Akt1; the phosphorylation of the homologous residue in Akt2 (Ser131) has never been analyzed. Here we show that Akt2, endogenously or ectopically expressed in different cell lines, is not phosphorylated on Ser131 by CK2, while in vitro recombinant Akt2 is a CK2 substrate. These data support the hypothesis that in vivo a steric hindrance occurs which prevents the access to the CK2 site. Additionally, we have found that Ser129 phosphorylation is involved in the recognition of the Akt1-specific substrate palladin; this observation provides an explanation of why Akt2, lacking Ser131 phosphorylation in the linker region, has a low efficiency in targeting palladin. CK2-dependent phosphorylation is therefore a crucial event which, discriminating between Akt1 and Akt2, can account for different substrate specificity, and, more in general, for fine tuning of Akt activity in the control of isoform-dependent processes.},
  author       = {Girardi, Cristina and James, Peter and Zanin, Sofia and Pinna, Lorenzo A and Ruzzene, Maria},
  issn         = {0006-3002},
  language     = {eng},
  number       = {9},
  pages        = {1865--1874},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta},
  title        = {Differential phosphorylation of Akt1 and Akt2 by protein kinase CK2 may account for isoform specific functions.},
  url          = {http://dx.doi.org/10.1016/j.bbamcr.2014.04.020},
  volume       = {1843},
  year         = {2014},
}