Phosphorylation of synthetic fragments of inhibitor‐2 of protein phosphatase‐1 by casein kinase‐1 and ‐2

Marin, Oriano; Meggio, Flavio; Sarno, Stefania; Andretta, Monica; Pinna, Lorenzo A.

doi:10.1111/j.1432-1033.1994.tb19037.x

Cited by 55 publications

(46 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The spectral analysis revealed another doubly charged (2 þ ) signal at m/z 823.27, identified as the same 115-128 peptide that was modified with two phosphate groups at levels of both S122 and S125, with no modifications seen on S120. The phosphomodification on S122 occurs outside of the consensus sequence, a phenomenon that has been described for other casein kinase substrates (Marin et al, 1994(Marin et al, , 2003.…”

Section: Resultsmentioning

confidence: 67%

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Garzia¹,

D’Angelo²,

Amoresano

et al. 2007

Oncogene

View full text Add to dashboard Cite

The combination of an increase in the cAMP-phosphodiesterase activity of h-prune and its interaction with nm23-H1 have been shown to be key steps in the induction of cellular motility in breast cancer cells. Here we present the molecular mechanisms of this interaction. The region of the nm23-h-prune interaction lies between S120 and S125 of nm23, where missense mutants show impaired binding; this region has been highly conserved throughout evolution, and can undergo serine phosphorylation by casein kinase I. Thus, the casein kinase I d-e specific inhibitor IC261 impairs the formation of the nm23-hprune complex, which translates 'in vitro' into inhibition of cellular motility in a breast cancer cellular model. A competitive permeable peptide containing the region for phosphorylation by casein kinase I impairs cellular motility to the same extent as IC261. The identification of these two modes of inhibition of formation of the nm23-H1-h-prune protein complex pave the way toward new challenges, including translational studies using IC261 or this competitive peptide 'in vivo' to inhibit cellular motility induced by nm23-H1-h-prune complex formation during progression of breast cancer.

show abstract

Section: Resultsmentioning

confidence: 67%

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Garzia¹,

D’Angelo²,

Amoresano

et al. 2007

Oncogene

View full text Add to dashboard Cite

show abstract

“…Analysis of the sequence surrounding Ser-45 in ␤-catenin does not reveal the well-known features of the consensus sequence that are generally recognized by CK1 in a variety of proteins and peptides that serve as its substrates. This canonical consensus depends on the presence of a side chain containing a negative charge derived from either a phosphoamino acid or one or more acidic residues at position nϪ3 relative to the target serine or threonine (2,21,24). These features are absent in the sequence surrounding Ser-45 of ␤-catenin.…”

Section: Discussionmentioning

confidence: 99%

“…The APC peptides contain the sequence of the human APC protein from residues 1275 to 1290 or mutants with a sequence RRRA attached to its amino end. Peptides from ␤-casein and protein phosphatase 1 inhibitor-2 had been studied (21,24). All other peptides contain three arginines in their amino terminus to facilitate the phosphocellulose paper assay.…”

Section: Resultsmentioning

confidence: 99%

“…This consensus is D͞E X X S͞T for unprimed substrates or S͞T-PO4 X X S͞T for primed targets. It must be noted, however, that whereas CK2 carboxylic and phosphorylated side chains are equally potent as specificity determinants, CK1 by far prefers phosphorylated determinants, needing otherwise multiple acidic residues upstream from position nϪ2 to achieve catalytic efficiency comparable to that of primed sites (21,24).…”

Section: Ck1mentioning

confidence: 99%

See 1 more Smart Citation

A noncanonical sequence phosphorylated by casein kinase 1 in β-catenin may play a role in casein kinase 1 targeting of important signaling proteins

Marin

Bustos

Cesaro

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

130

115

View full text Add to dashboard Cite

Protein kinase casein kinase 1 (CK1) phosphorylates Ser-45 of ␤-catenin, ''priming'' the subsequent phosphorylation by glycogen synthase-3 of residues 41, 37, and 33. This concerted phosphorylation of ␤-catenin signals its degradation and prevents its function in triggering cell division. The sequence around Ser-45 does not conform to the canonical consensus for CK1 substrates, which prescribes either phosphoamino acids or acidic residues in position n؊3 from the target serine. However, the ␤-catenin sequence downstream from Ser-45 is very similar to a sequence recognized by CK1 in nuclear factor for activated T cells 4. The common features include an SLS motif followed two to five residues downstream by a cluster of acidic residues. Synthetic peptides reproducing residues 38 -65 of ␤-catenin were assayed with purified rat liver CK1 or recombinant CK1␣ and CK1␣L from zebrafish. The results demonstrate that SLS and acidic cluster motifs are crucial for CK1 recognition. Pro-44 and Pro-52 are also important for efficient phosphorylation. Similar results were obtained with the different isoforms of CK1. Phosphorylation of mutants of full-length recombinant ␤-catenin from zebrafish confirmed the importance of the SLS and acidic cluster motifs. A search for proteins with similar motifs yielded, among other proteins, adenomatous polyposis coli, previously found to be phosphorylated by CK1. There is a strong correlation of ␤-catenin mutations found in thyroid tumors with the motifs recognized by CK1 in this protein.consensus sequence ͉ nuclear factor for activated T cells 4 ͉ adenomatous polyposis coli ͉ Wnt signaling ͉ thyroid tumor mutations

show abstract

“…In addition, this peptide sequence has a Glu residue at the Ϫ3 position NH 2 -terminal to the target Ser 363 and satisfies the CKI consensus sequence requirement for an acidic residue, three residues to the amino-terminal side of the target Ser/Thr (26). Although CKI and CKII have distinctive substrate preferences, several proteins are reported to be phosphorylated by both CKII and CKI in vitro at the same site (38). To examine whether Ser 363 in Cx45.6 can be phosphorylated by CKI or/and CKII, we performed in vitro phosphorylation by CKI/CKII with the peptide RRRE 358 EEVVS 363 DEVE 367 .…”

Section: Phosphorylation Of a Peptide Corresponding To Amino Acidsmentioning

confidence: 99%

Casein Kinase II Phosphorylates Lens Connexin 45.6 and Is Involved in Its Degradation

Yin¹,

Jedrzejewski²,

Jiang³

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Connexin (Cx) 45.6, an avian counterpart of rodent Cx50, is phosphorylated in vivo, but the sites and function of the phosphorylation have not been elucidated. Our peptide mapping experiments showed that the Ser 363 site in the carboxyl (COOH) terminus of Cx45.6 was phosphorylated and that this site is within casein kinase (CK) II consensus sequence, although showing some similarity to CKI sequence. The peptide containing Ser 363 could be phosphorylated in vitro by CKII, but not by CKI. Furthermore, CKII phosphorylated Cx45.6 in embryonic lens membrane and the fusion protein containing the COOH terminus of Cx45.6. Two-dimensional peptide mapping experiments showed that one of the Cx45.6 peptides phosphorylated in vivo migrated to the same spot as one of those phosphorylated by CKII in vitro. Furthermore, CKII activity could be detected in lens lysates. To assess the function of this phosphorylation event, exogenous wild type and mutant Cx45.6 (Ser 363 3 Ala) were expressed in lens primary cultures by retroviral infection. The mutant Cx45.6 was shown to be more stable having a longer half-life compared with wild type Cx45.6. Together, the evidence suggests that CKII is likely a kinase responsible for the Ser 363 phosphorylation, leading to the destablization and degradation of Cx45.6. The connexin degradation induced by phosphorylation has a broad functional significance in the regulation of gap junctions in vivo.Gap junctions are channels between two adjacent cells, which allow passage of small molecules (M r Յ 1000) such as small metabolites, ions, and second messengers. The gap junction-mediated cell-to-cell communications are important in maintaining cell and tissue functions (1). The structural components of gap junctions are members of a family of related membrane proteins called connexins, which consist of four conserved transmembrane domains and two extracellular loops, while their cytoplasmic regions are unique. The COOH terminus, the most variable region among connexins, contains several putative kinase consensus sequences. The phosphorylation of connexins has been indicated in the intracellular trafficking of connexins (2), channel assembly (3

show abstract

Phosphorylation of synthetic fragments of inhibitor‐2 of protein phosphatase‐1 by casein kinase‐1 and ‐2

Cited by 55 publications

References 33 publications

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

Phosphorylation of nm23-H1 by CKI induces its complex formation with h-prune and promotes cell motility

A noncanonical sequence phosphorylated by casein kinase 1 in β-catenin may play a role in casein kinase 1 targeting of important signaling proteins

Casein Kinase II Phosphorylates Lens Connexin 45.6 and Is Involved in Its Degradation

Contact Info

Product

Resources

About