The salt bridge of calcineurin is important for transferring the effect of CNB binding to CNA

Hou, Qiang; Yi, Xiang; Jiang, Guangde; Wang, Qun

doi:10.1016/j.febslet.2004.10.002

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…It is known that both CnB and Ca 2 þ /CaM are important to activate phosphatase activity of CaN (Klee et al, 1988), but here we found that CaM could compete for the binding of c-Jun to CaN (Figure 3b). According to previous report, CnB alone, but not CaM, is able to activate the phosphatase activity of CaN by about 10-fold, and synergistic activation can be observed when CnA interacts with both CnB and Ca 2 þ /CaM (Hou et al, 2004). Therefore, we speculate that CnB may compensate for the partial loss of CaN activity as a result of the competitive binding between CaM and c-Jun to CaN.…”

Section: Discussionmentioning

confidence: 95%

Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

et al. 2007

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Section: Discussionmentioning

confidence: 95%

Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

et al. 2007

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“…Interestingly, the crystal structure revealed considerable contacts of the CaN R N-terminus with Ca 2+ binding motif 3 of the B subunit, suggesting a role in CaNB binding and thus regulation of phosphatase activity. Additionally, it was proposed that the formation of a salt bridge between Glu53 of CaNA R and Lys134 of CaNB contributes to a conformational change in the catalytic subunit leading to the activation of CaN (53). The loss of phosphatase activity after proteolytic removal of the CaN R N-terminus also suggests an involvement in the regulation of the active site (19).…”

Section: Discussionmentioning

confidence: 99%

The Proline-Rich N-Terminal Sequence of Calcineurin Aβ Determines Substrate Binding

et al. 2009

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Three different genes of catalytic subunit A of the Ca(2+)-dependent serine/threonine protein phosphatase calcineurin (CaN) are encoded in the human genome forming heterodimers with regulatory subunit B. Even though physiological roles of CaN have been investigated extensively, less is known about the specific functions of the different catalytic isoforms. In this study, all human CaN holoenzymes containing either the alpha, beta, or gamma isoform of the catalytic subunit (CaN alpha, beta, or gamma, respectively) were expressed for the first time. Comparative kinetic analysis of the dephosphorylation of five specific CaN substrates provided evidence that the distinct isoforms of the catalytic subunit confer substrate specificities to the holoenzymes. CaN alpha dephosphorylates the transcription factor Elk-1 with 7- and 2-fold higher catalytic efficiencies than the beta and gamma isoforms, respectively. CaN gamma exhibits the highest k(cat)/K(m) value for DARPP-32, whereas the catalytic efficiencies for the dephosphorylation of NFAT and RII peptide were 3- and 5-fold lower, respectively, when compared with the other isoforms. Elk-1 and NFAT reporter gene activity measurements revealed even more pronounced substrate preferences of CaNA isoforms. Moreover, kinetic analysis demonstrated that CaN beta exhibits for all tested protein substrates the lowest K(m) values. Enzymatic characterization of the CaN beta(P14G/P18G) variant as well as the N-terminal truncated form CaN beta(22-524) revealed that the proline-rich sequence of CaN beta is involved in substrate recognition. CaN beta(22-524) exhibits an at least 4-fold decreased substrate affinity and a 5-fold increased turnover number. Since this study demonstrates that all CaN isoforms display the same cytoplasmic subcellular distribution and are expressed in each tested cell line, differences in substrate specificities may determine specific physiological functions of the distinct isoforms.

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“…Research also shows that BBH and the N-terminus are mainly responsible for the interaction with CNB. Work in our laboratory has also shown that a salt bridge between Glu53 and Lys134 plays an important role in stabilizing the dimeric structure [25] . The CBD contains an amphipathic helix that interacts with the hydrophobic region of CaM.…”

Section: Figurementioning

confidence: 97%

Recent progress on the structure of Ser/Thr protein phosphatases

2008

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PP1, PP2A and PP2B, belonging to the PPP family of Ser/Thr protein phosphatases, participate in regulating many important physiological processes, such as cell cycle control, regulation of cell growth and division regulation, etc. The sequence homology between them is relatively high, and tertiary structure is conserved. Because of the complexity of the structure of PP2A and the diversity of its regulatory subunits, its structure is less well known than those of PP1 and PP2B. The PP2A holoenzyme consists of a heterodimeric core enzyme, comprising a scaffolding subunit and a catalytic subunit, as well as a variable regulatory subunit. In this study, the subunit compositions, similarities and differences between the Ser/Thr protein phosphatases structures are summarized.

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The salt bridge of calcineurin is important for transferring the effect of CNB binding to CNA

Cited by 7 publications

References 22 publications

Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

Calcineurin-mediated dephosphorylation of c-Jun Ser-243 is required for c-Jun protein stability and cell transformation

The Proline-Rich N-Terminal Sequence of Calcineurin Aβ Determines Substrate Binding

Recent progress on the structure of Ser/Thr protein phosphatases

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