ライフサイエンスコーパス: PTPalpha

1 PTPalpha display modest peptide substrate selectivity an

2 PTPalpha knockout (PTPalpha(-/-)) mice are viable and di

3 PTPalpha(-/-) and WT mice were tested for anxiety, swimm

4 PTPalpha(-/-) mice have more oligodendrocyte lineage cel

5 PTPalpha(-/-) mice showed decreased exploratory locomoto

6 PTPalpha(-/-) mice were indistinguishable from WT in swi

7 Tyr789-->Phe mutation abrogates PTPalpha-Src binding, dephosphorylation of pTyr527 (alth

8 nvolving protein tyrosine phosphatase alpha (PTPalpha) and translocation of CSK and predicts a specif

9 role of protein-tyrosine phosphatase alpha (PTPalpha) in regulating signaling by the ErbB2 oncoprote

10 ylation, protein tyrosine phosphatase alpha (PTPalpha) is activated by two different mechanisms durin

11 Protein tyrosine phosphatase alpha (PTPalpha) is believed to dephosphorylate physiologically

12 Protein tyrosine phosphatase alpha (PTPalpha) is essential for Fyn kinase activation, and we

13 icity of protein-tyrosine phosphatase alpha (PTPalpha) is primarily controlled by the membrane proxim

14 Protein tyrosine phosphatase alpha (PTPalpha) promotes integrin-stimulated cell migration in

15 Protein-tyrosine phosphatase alpha (PTPalpha) promotes OPC differentiation, but its role in

16 strated a direct interaction between FAK and PTPalpha, which was dependent on the FAT domain of FAK a

17 teractions between the FAT domain of FAK and PTPalpha.

18 r all phosphatases tested except for LAR and PTPalpha.

19 in tyrosine phosphatases (PTPases) PTP1B and PTPalpha are known to dephosphorylate the insulin recept

20 It thereby activates Src, and PTPalpha overexpression neoplastically transforms NIH 3T

21 kinases such as Src kinase and PTPs such as PTPalpha and PTPepsilon modulate the activity of delayed

22 n disrupt PTPalpha-Src binding and can block PTPalpha-mediated dephosphorylation and activation in pr

23 hotyrosine), the minimal sizes recognized by PTPalpha are either ADEpYLI or DADEpY-NH2.

24 g protein suggests that RACK1 may coordinate PTPalpha-Tyr-789 phosphorylation in these signaling netw

25 dicted by the model, catalytically defective PTPalpha has reduced Src binding in vivo.

26 to enable IGF-1-stimulated and Abl-dependent PTPalpha-Tyr-789 phosphorylation.

27 we find that excess SH2 domains can disrupt PTPalpha-Src binding and can block PTPalpha-mediated dep

28 is explains why the substitutions eliminated PTPalpha transforming activity, even though PTPalpha int

29 is phosphorylation also specifically enables PTPalpha to dephosphorylate pTyr527.

30 inhibitor is 180 nM for PTP1B and 10 mM for PTPalpha in vitro.

31 ctively, these results reveal a new role for PTPalpha in the regulation of motility of mammary epithe

32 ing Yersinia PTPase, SHP1, SHP2, LAR, HePTP, PTPalpha, CD45, VHR, MKP3, Cdc25A, Stp1, and PP2C).

33 t src and fyn activity is reduced to <50% in PTPalpha(-/-) mice.

34 p27Kip1 accumulation, and Rho inhibition in PTPalpha-deficient cells restored expression of p27Kip1.

35 Src is not activated in mitosis in PTPalpha-knockout cells, indicating a unique mitotic rol

36 pTyr789 in PTPalpha is constitutively phosphorylated and binds Grb2

37 Thus, in addition to increasing PTPalpha nonspecific catalytic activity, Ser180 and Ser2

38 n SFK-deficient cells switches IGF-1-induced PTPalpha phosphorylation to occur in an Abl-independent

39 This is in contrast to integrin-induced PTPalpha phosphorylation, that induced by IGF-1 can occu

40 binds Grb2, an interaction that may inhibit PTPalpha activity.

41 PTPalpha knockout (PTPalpha(-/-)) mice are viable and display no gross abno

42 During Morris water maze (MWM) learning, PTPalpha(-/-) mice had increased latencies to reach the

43 On the molecular level, PTPalpha-deficient mouse OPCs and rat CG4 cells have dec

44 found that RNA interference (RNAi)-mediated PTPalpha knockdown in the DMS reduces excessive ethanol

45 e caused by overexpression of PTP1B (but not PTPalpha) was reversed by treating the transfected cells

46 ation specifically eliminated the ability of PTPalpha to dephosphorylate and activate Src even during

47 to increase cell motility in the absence of PTPalpha was characterized by prolonged interaction of G

48 may participate in the mitotic activation of PTPalpha and Src and that there are intramolecular inter

49 The activation of PTPalpha, combined with the effects of mitotic Cdc2-medi

50 of PTPalpha, suggesting that attenuation of PTPalpha activity may contribute to enhanced ErbB2 signa

51 mbrane-distal cytoplasmic PTP domain (D2) of PTPalpha: the direct intramolecular regulation of the ac

52 The membrane distal (D2) domain of PTPalpha by itself is a genuine PTPase, possessing catal

53 tact membrane-proximal phosphatase domain of PTPalpha.

54 Furthermore, downregulation of PTPalpha in the DMS of mice significantly reduces ethano

55 ntegrin signaling, and our identification of PTPalpha as a RACK1 binding protein suggests that RACK1

56 f ErbB2 led to the transient inactivation of PTPalpha, suggesting that attenuation of PTPalpha activi

57 Here we report that loss of PTPalpha enhanced in vitro proliferation and survival an

58 red without change in the phosphorylation of PTPalpha at Tyr789, which is required for "phosphotyrosi

59 ng SFKs, IGF-1-stimulated phosphorylation of PTPalpha is mediated by RACK1 but is Abl-independent.

60 Recruitment of PTPalpha to focal adhesions, IL-1-induced Ca(2+) release

61 ivation is facilitated by the recruitment of PTPalpha to synaptic membranes, the compartment where Fy

62 required for IL-1-mediated sequestration of PTPalpha to focal adhesions.

63 Furthermore, RNAi-induced suppression of PTPalpha led to increased cell migration in an ErbB2-dep

64 Finally, suppression of PTPalpha resulted in increased phosphorylation of focal

65 a lipid raft-preferring chimeric version of PTPalpha fail to reconstitute antigen-dependent Fcepsilo

66 inhibitor, overexpression of either PTP1B or PTPalpha caused a significant decrease in the amount of

67 cted by electroporation with either PTP1B or PTPalpha were treated without or with the inhibitor, and

68 istance caused by overexpression of PTP1B or PTPalpha.

69 d neoplastic transformation by overexpressed PTPalpha in vivo.

70 We show that four PTPs (TCPTP, Shp2, PEST, PTPalpha) are capable of rescuing the effects of v-Src t

71 excluded transmembrane tyrosine phosphatase, PTPalpha, suppresses Lyn kinase activity and markedly re

72 ds activated the receptor-like phosphatases, PTPalpha and LAR.

73 part through the role of Src-phosphorylated PTPalpha-Tyr(P)-789 in recruiting and localizing p130Cas

74 Together, these results position PTPalpha upstream of Fyn within the DMS and demonstrate

75 ignal transduction pathway, including PTP1B, PTPalpha, and LAR.

76 Receptor PTPalpha is a widely expressed transmembrane enzyme enri

77 d that RACK1 coordinates the IGF-1 receptor, PTPalpha, and Abl in a complex to enable IGF-1-stimulate

78 along with Tyr789 phosphorylation) regulates PTPalpha substrate specificity.

79 The growth factor IGF-1 also stimulates PTPalpha-Tyr-789 phosphorylation to positively regulate

80 unknown kinase distinct from SFKs can target PTPalpha.

81 We found that PTPalpha binds to the scaffold protein RACK1 and that RA

82 Here we tested the hypothesis that PTPalpha in the DMS is part of the Fyn/GluN2B pathway an

83 e mitotic activation of Src, indicating that PTPalpha is the membrane-bound, serine phosphorylation-a

84 We propose that PTPalpha-Fyn signaling negatively regulates OPC prolifer

85 The data suggest that PTPalpha serves a regulatory function in learning and ot

86 are intramolecular interactions between the PTPalpha C-terminal and membrane-proximal regions that a

87 r, the effect of the loss of function of the PTPalpha gene on behavior has yet to be investigated.

88 PTPalpha transforming activity, even though PTPalpha interphase dephosphorylation of nonspecific sub

89 Thus, PTPalpha acts in OPCs to limit self-renewal and facilita

90 Binding of certain of these compounds to PTPalpha disrupts D1-D2 basal state contacts and allows

91 regulates IGF-1/IGF-1 receptor signaling to PTPalpha.

92 n and causes a mitotic increase in transient PTPalpha-Src binding.

93 veral exhibit selectivities for PTP1B versus PTPalpha, LAR, and VHR that are greater than 2 orders in

94 s, including PTP1B, YopH, CD45, Cdc25A, VHR, PTPalpha, and LAR, to identify compounds with improved p

95 ein kinase C-mediated phosphorylation within PTPalpha.