ライフサイエンスコーパス: betaARK

1 beta-Adrenergic receptor kinase 1 (betaARK 1 or GRK2) mediates desensitization of photorela

2 erially expressed PH domains of Sos1, IRS-1, betaARK, and PLCdelta1 were analyzed functionally by mea

3 Whereas the PH domains from IRS-1, betaARK, or PLCdelta1 did not show any effect in the ooc

4 However, a betaARK phosphorylation-impaired beta2AR mutant (Y326A)

5 forskolin-induced contractile response in a betaARK-ct sensitive manner.

6 Although overexpression of a betaARK inhibitor in hearts of transgenic mice did not a

7 protein tubulin could specifically bind to a betaARK-coupled affinity column.

8 ration, we examined the relationship between betaARK and/or beta-arrestin expression and beta2AR sequ

9 ired the simultaneous overexpression of both betaARK and beta-arrestin for this to occur.

10 in steady-state levels and activity of both betaARK and GRK6.

11 ility of the beta2AR to be phosphorylated by betaARK or to interact normally with beta-arrestin subst

12 ver, inhibiting beta(2)AR phosphorylation by betaARK C terminus or dephosphorylation by okadaic acid

13 omoted desensitization or phosphorylation by betaARK.

14 ntiating effects are completely prevented by betaARK-ct, a peptide inhibitor of beta-adrenergic recep

15 est not only that the complement of cellular betaARK and arrestin proteins synergistically regulate b

16 minus of beta-adrenergic receptor kinase (ct-betaARK), an inhibitor Gbetagamma signaling, prevented g

17 Expression of ct-betaARK also prevented Src-mediated tyrosine phosphoryla

18 onses were inhibited by the expression of ct-betaARK.

19 evated GRK6 protein levels, while decreasing betaARK expression.

20 body and interleukin-2) resulted in enhanced betaARK and GRK6 mRNA and protein levels and increased a

21 To evaluate betaARK and beta-arrestin regulation of beta2AR sequestr

22 alpha2C4 without or with the following GRKs: betaARK, betaARK2, GRK5, or GRK6.

23 eneralized response to cellular hypertrophy, betaARK activity was measured in transgenic mice homozyg

24 marked cardiac hypertrophy, no difference in betaARK activity was found in these mice overexpressing

25 due to significant cell-type differences in betaARK expression and/or function.

26 n in IRS proteins, because the PH domains in betaARK, phospholipase Cgamma, or spectrin did not bind

27 he lung and indeed revealed heterogeneity in betaARK gene expression.

28 The mechanism for the increase in betaARK activity appears not to be related to the induct

29 otype, consistent with the lack of increased betaARK levels in Galphaq mice.

30 lation of the receptor by the betaAR kinase (betaARK) or other closely related G protein-coupled rece

31 onist-dependent manner is the betaAR kinase (betaARK), a member of the family of G protein-coupled re

32 the carboxyl terminus of the betaAR kinase (betaARK), which acts to inhibit the kinase, or concomita

33 ner for the beta-adrenergic receptor kinase (betaARK or GRK-2), which was shown to have Arf-GAP activ

34 gulation of beta-adrenergic receptor kinase (betaARK) and GRK6 expression and activity in myelomonocy

35 tion by the beta-adrenergic receptor kinase (betaARK) facilitates subsequent interaction with an arre

36 lthough the beta-adrenergic receptor kinase (betaARK) mediates agonist-dependent phosphorylation and

37 tion of the beta-adrenergic receptor kinase (betaARK) phosphorylation sites in the third intracellula

38 itor of the beta-adrenergic receptor kinase (betaARK), an enzyme that phosphorylates and uncouples ag

39 cluding the beta-adrenergic receptor kinase (betaARK), was found to bind to various phospholipids as

40 tely to the beta-adrenergic receptor kinase (betaARK).

41 terminus of beta-adrenergic receptor kinase (betaARK-ct), and N17Ras inhibited shear-dependent activa

42 At the protein level, betaARK expression in airway smooth muscle cells was nea

43 Overexpression of beta-arrestin, but not betaARK, in COS cells increased the extent of wild-type

44 During our attempts to identify novel betaARK interacting proteins, we found that the cytoskel

45 previously that the membrane association of betaARK (beta-adrenergic receptor kinase) (GRK2) is medi

46 s bind GRKs, whereas the catalytic domain of betaARK contains the primary tubulin binding determinant

47 ificant cell-type variation in expression of betaARK and that such variation is directly related to t

48 as imparted to alpha2C10 by co-expression of betaARK but not GRK6, while alpha2C4 failed to desensiti

49 failed to desensitize with co-expression of betaARK.

50 brain tissue; (ii) co-immunoprecipitation of betaARK and tubulin from COS-1 cells; and (iii) co-local

51 To determine whether the induction of betaARK occurred because of a generalized response to ce

52 Because inhibition of betaARK activity is pivotal for amelioration of cardiac

53 e transfer of the beta2AR or an inhibitor of betaARK-mediated desensitization can potentiate beta-adr

54 s with cell lines revealed that the level of betaARK mRNA in airway smooth muscle cells was approxima

55 om COS-1 cells; and (iii) co-localization of betaARK and GRK5 with microtubule structures in COS-1 ce

56 stration correlated best with the product of betaARK and beta-arrestin expression.

57 ted by the following: (i) co-purification of betaARK with tubulin from brain tissue; (ii) co-immunopr

58 ts desensitization by increasing the rate of betaARK phosphorylation of the betaAR.

59 Gbetagamma signaling with pertussis toxin or betaARK-ct, a peptide inhibitor of Gbetagamma, completel

60 her the beta2AR (Adeno-beta2AR) or a peptide betaARK inhibitor (consisting of the carboxyl terminus o

61 xpression of Gbetagamma-sequestering peptide betaARK-ct could not prevent betaAR desensitization or c

62 s, five members of the GRK family bind PIP2, betaARK (GRK2), betaARK2 (GRK3), GRK4, GRK5, and GRK6.

63 sion of two betagamma sequestering proteins (betaARK-ct and alphat) prevented IL-8 receptor type B-me

64 These data demonstrate that betaARK and GRK6 expression are differentially regulated

65 In vitro analysis demonstrated that betaARK and G protein-coupled receptor kinase-5 (GRK5) w

66 bryonic kidney (HEK) 293 cells indicate that betaARK and arrestin proteins (beta-arrestins) also regu

67 Taken together, these data suggest that betaARK is a central molecule involved in alterations of

68 n of the PIP2 binding site distinguishes the betaARK (GRK2 and GRK3) and GRK4 (GRK4, GRK5, and GRK6)

69 Expression of the betaARK inhibitor had no effect on the phenotype, consis

70 tagamma inhibitor (glutathione S-transferase-betaARK) inhibited IGF-I and lysophosphatidic acid-stimu

71 [1alpha,25(OH)2-vitamin D3] lineage, whereas betaARK protein levels and activity were only slightly a

72 ertussis toxin or scavenging Gbetagamma with betaARK-ct overexpression could not prevent beta(2)-AR-i