ライフサイエンスコーパス: ERK3

1 s promoted increased nuclear accumulation of Erk3.

2 physiological substrate of the atypical MAPK ERK3.

3 he cleavage and nuclear translocation of GFP-ERK3.

4 MEK2 but not MEK1 will phosphorylate ERK3.

5 ants to the mitogen-activated protein kinase ERK3.

6 , it does lead to constitutive activation of ERK3.

7 nd that DUSP2 can also regulate the atypical ERK3/4-MK5 signalling pathway in mammalian cells.

8 c antisera identified serine 189, within the Erk3 activation loop, as a site directly phosphorylated

9 sal link between PKC beta overexpression and ERK3 activation was established because 12-O-tetradecano

10 cetate treatment down-regulated both PKC and ERK3 activities in both PKC beta 1 transfectants.

11 However, a > 10-fold increase in ERK3 activity in each PKC beta transfectant was shown by

12 ERK3 activity was found in nuclear and membrane fraction

13 e specificity of the ERK3 kinase, mutants of ERK3 and ERK2 were made in which the phosphorylated resi

14 main within the carboxyl-terminal domains of ERK3 and ERK4 and the conserved kinase interaction motif

15 rect and results in the dephosphorylation of ERK3 and ERK4 and the stabilization of DUSP2.

16 The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a seri

17 ude that MK5 activation is dependent on both ERK3 and ERK4 in these cells and that these atypical MAP

18 However, the regulation of ERK3 and ERK4 phosphorylation and activity is poorly und

19 emonstrate that expression of DUSP2 inhibits ERK3 and ERK4-mediated activation of its downstream subs

20 the MKP family in being able to bind to both ERK3 and ERK4.

21 Complex formation between ERK3 and MK5 results in phosphorylation and activation o

22 ivation of MK5, concomitant stabilization of ERK3, and the nuclear exclusion of both proteins.

23 This approach identified the atypical MAPK Erk3 as a potential Pak2 substrate.

24 We found that in comparison with wild type ERK3, both L290P and L290V mutants have greatly increase

25 all interfering RNAs targeting both ERK4 and ERK3 causes a further reduction in the MK5 activity by m

26 The ERK3 cDNA predicts a protein of 62,000 in size with a C-

27 sed in vitro kinase assays using recombinant Erk3 confirmed the protein microarray results, and phosp

28 espite marked similarities to ERK1 and ERK2, ERK3 does not phosphorylate typical MAP kinase substrate

29 ras between ERK2 and the catalytic domain of ERK3 (ERK3DeltaC), and some mutants of these chimeras, t

30 However unlike ERK3, ERK4 is a stable protein, and its half-life is not

31 ERK3, ERK5 and ERK7 are other MAPKs that have distinct r

32 Recombinant ERK3 expressed in mammalian cells or in bacteria is a pr

33 at its C terminus are deleted, the resulting ERK3 fragment of 45 kDa is still found primarily in the

34 llowing: 1) the N-terminal folding domain of ERK3 functions in phosphoryl transfer reactions with the

35 nt studies have revealed important roles for ERK3 in cancers.

36 ps accounting for constitutive activation of ERK3 in cells with elevated levels of PKC beta 1 or PKC

37 However, ablation of ERK3 in HeLa cells using small interfering RNA or in fib

38 udy identifies a previously unknown role for ERK3 in promoting lung cancer cell invasiveness by phosp

39 py examining the subcellular localization of ERK3 in several cell lines indicated that this enzyme wa

40 ed increased activity at 63 kDa, the size of ERK3, in each of two PKC beta 1 and each of two PKC beta

41 r the localization of an MAPK family member, ERK3, in which cell cycle-regulated, site-specific prote

42 The double mutant S189T,G191Y ERK3, in which the phosphorylated residues from ERK2 rep

43 Here, we report that ERK3 interacted with and phosphorylated steroid receptor

44 ERK3 is an atypical mitogen-activated protein kinase (MA

45 locates to the nucleus following activation, ERK3 is constitutively localized to the nucleus, despite

46 ERK3 is most similar in its kinase catalytic domain to E

47 evealed that the subcellular localization of ERK3 is temporally regulated.

48 regions of the C-terminal tail revealed that ERK3 is the expected size and is ubiquitously expressed

49 Extracellular signal-regulated kinase 3 (ERK3) is a member of the mitogen-activated protein (MAP)

50 PKC beta does not lead to overexpression of ERK3, it does lead to constitutive activation of ERK3.

51 hough the ERK3 kinase is highly specific for ERK3, it does not recognize tyrosine, a feature that dis

52 residues in ERK3, was phosphorylated by the ERK3 kinase but only on threonine.

53 The ERK3 kinase did not phosphorylate ERK2 or ERK2 mutants.

54 These findings indicate that although the ERK3 kinase is highly specific for ERK3, it does not rec

55 This ERK3 kinase phosphorylated a single site on ERK3, Ser189

56 To test the specificity of the ERK3 kinase, mutants of ERK3 and ERK2 were made in which

57 nctionally and mechanistically characterized ERK3 L290P/V mutations, which are located within ERK3's

58 r findings suggest that L290P/V mutations of ERK3 may confer increased invasiveness to cancers.

59 This ERK3-mediated phosphorylation at S857 was essential for

60 t was shown by immunoprecipitation with anti-ERK3 monoclonal antibody followed by either immune compl

61 lotting and by immunoprecipitation with anti-ERK3 monoclonal antibody.

62 Little is known, however, regarding ERK3 mutations in cancers.

63 terfering RNA or in fibroblasts derived from ERK3 null mice reduces the activity of endogenous MK5 by

64 Importantly, knockdown of ERK3 or SRC-3 inhibited the ability of lung cancer cells

65 osphorylation and inhibited the formation of Erk3-Prak complexes.

66 ERK3 promotes cancer cell migration/invasion and tumor m

67 Collectively, our results identify the Erk3 protein as a novel class I Pak substrate and furthe

68 Erk3 protein is known to shuttle between the cytoplasm a

69 As such, ERK3 protein kinase may be an attractive target for ther

70 The ERK3 protein kinase was immunologically distinct from mi

71 Here we identify the ERK3-related kinase ERK4 as a bona fide interaction part

72 inases (MEK) 1 and 2 which phosphorylate the ERK3-related MAP kinases ERK1 and ERK2.

73 n kinase activity, L290P/V mutations enhance ERK3's cytoplasmic localization by increasing the intera

74 L290P/V mutations, which are located within ERK3's kinase domain, and are shown to exist in several

75 tion and invasion, but have little impact on ERK3's role in cell proliferation.

76 ERK3 kinase phosphorylated a single site on ERK3, Ser189, comparable to Thr183, one of the two activ

77 gulation and substrates of the atypical MAPK ERK3 signaling cascade and its function in cancer progre

78 p97 is a class III ERP, related to ERK3, that associates with AP-1 DNA without AP-1 protein

79 analysis of green fluorescent protein (GFP)-ERK3 uncovered a nuclear form that was carboxy-terminall

80 ERK3, unlike the MAP kinases ERK1 and ERK2, is localized

81 ERK3 was expressed at equal abundance in PKC beta 1, PKC

82 In addition, ERK3 was found to be highly upregulated in human lung ca

83 rom ERK2 replaced the comparable residues in ERK3, was phosphorylated by the ERK3 kinase but only on

84 f the MAP kinase ERK2 and the related kinase ERK3 which are modified in the phosphorylation loop.

85 Ser189 of ERK3, which corresponds to Thr183, one of the activating