ライフサイエンスコーパス: HCK

1 HCK expression was significantly upregulated in response

2 HCK represents a novel target for therapeutic developmen

3 HCK-knockout (KO) or HCK-inhibitor decreases macrophage

4 HCKs grown in vitro were stimulated with IL-1alpha, TNF-

5 HCKs incubated with TNF-alpha, IL-1alpha, or IFN-gamma r

6 factor SPIB or EHF is sufficient to activate HCK-dependent apical-to-basolateral transcytosis of thes

7 Activated HCK subsequently phosphorylated PLCgamma2, which propaga

8 However, CDK2 and HCK kinase in complex with other flavone inhibitors such

9 oplasmic Src-family tyrosine kinases FGR and HCK and related signaling proteins.

10 Mutated MYD88 triggers BTK, IRAK1/IRAK4, and HCK growth and survival signaling, whereas CXCR4 mutatio

11 ive interaction interface between NLRP12 and HCK, suggesting that HCK likely binds NLRP12 in the regi

12 is significantly enhanced in both HCECs and HCKs in response to either IL-1alpha or TNF-alpha stimul

13 Cultures of HCECs and HCKs were stimulated with either human recombinant IL-1a

14 We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, i

15 e more potent HCK inhibitor A419259, blocked HCK activation and induced apoptosis in mutated MYD88 WM

16 man studies in B-cell malignancies driven by HCK and BTK.

17 an activating function in cells coexpressing HCK p59.

18 y, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammato

19 Here we find that high HCK levels correlate with reduced survival of colorectal

20 Overall, our work identifies HCK as a regulator of NLRP12-mediated PANoptosis, sugges

21 In addition, in HCK cell over-expressing LEDGF, the levels of hINV mRNA

22 intramolecular autoinhibitory interaction in HCK.

23 IP-10 synthesis is induced in HCKs by IL-1alpha, TNF-alpha, and IFN-gamma.

24 ast, induction of I-TAC and MIG synthesis in HCKs requires costimulation with IFN-gamma and either IL

25 tein tyrosine kinases, including JAK1, JAK3, HCK, epidermal growth factor receptor kinase, and insuli

26 l simian virus 40-transformed keratinocytes (HCK), was transactivated by LEDGF significantly.

27 determine whether human corneal keratocyte (HCKs) in culture synthesize these chemokines in response

28 ss levels between human corneal keratocytes (HCKs), fibroblasts (HCFs) and keratoconus cells (HKCs).

29 FAE model, we show that the tyrosine kinase HCK regulates apical-to-basolateral transcytosis of non-

30 re, we identified hematopoietic cell kinase (HCK) as a regulator of NLRP12-mediated PANoptosis.

31 iously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury pr

32 myeloid-specific hematopoietic cell kinase (HCK) enables activity of antagonistic anti-programmed ce

33 lls show enhanced hematopoietic cell kinase (HCK) transcription and activation, and that HCK is activ

34 SRC family kinase hematopoietic cell kinase (HCK) triggers hematological malignancies as a tumor cell

35 ily kinase (SFK), hematopoietic cell kinase (HCK), specifically in DCs in response to IL-6.

36 survival through hematopoietic cell kinase (HCK)-mediated activation of Bruton tyrosine kinase (BTK)

37 ent activation of hematopoietic cell kinase (HCK).

38 on, p.Tyr515*, in hematopoietic cell kinase (HCK).

39 s increased levels of the src-family kinases HCK and FGR.

40 We show here that the SFKs LYN, HCK, or FGR are overexpressed and activated in AML proge

41 ted that expression and/or activation of LYN/HCK occurs during disease progression.

42 Mechanistically, HCK ablation reprograms tumor-associated macrophages and

43 Mutant HCK lacking the C-terminal inhibitory tyrosine Tyr522 ex

44 Mutant HCK lacking the C-terminal inhibitory tyrosine Tyr522 ex

45 Dysregulation of mutant HCK was confirmed ex vivo in primary cells and in vitro

46 ted MYD88 expressing WM cells with a mutated HCK gatekeeper greatly increased the half maximal effect

47 sing LEDGF, but not detectable in the normal HCK cells or HCK cells transfected with vector.

48 at hINV protein is found in the cytoplasm of HCK cells over-expressing LEDGF, but not detectable in t

49 (551), which then bound to the SH2 domain of HCK.

50 nt study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization vi

51 Exposure of HCK to IL-1alpha stimulated a 10-fold increase in ENA-78

52 iologically important, as over-expression of HCK with LEDGF increases the expression of the endogenou

53 Pharmacological and genetic inhibition of HCK activity indicated that HCK is required for HCMV rea

54 namic studies showed sustained inhibition of HCK and BTK for 24 hours after single oral administratio

55 Meanwhile, therapeutic inhibition of HCK in humanized mice engrafted with patient-derived xen

56 tified KIN-8194 as a novel dual inhibitor of HCK and BTK.

57 and IL-6 transcription, whereas knockdown of HCK reduced survival and attenuated BTK, phosphoinositid

58 r study supports the specific requirement of HCK p59 and FGR src-family kinases for FCRL4-mediated im

59 esults suggest that therapeutic targeting of HCK activity enhances response to immunotherapy by simul

60 Treatment of HCKs with IFN-gamma activated STAT1 and, in combination

61 or STAT1 by IFN-gamma receptors expressed on HCKs was determined by Western blot analysis.

62 ut not detectable in the normal HCK cells or HCK cells transfected with vector.

63 xpression of IL-10 in the presence of FGR or HCK p59 in response to CpG, but increased levels of IFN-

64 HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammat

65 to identify and characterize the pathogenic HCK mutation.

66 Ibrutinib and the more potent HCK inhibitor A419259, blocked HCK activation and induce

67 We propose HCK-driven pulmonary and cutaneous vasculitis as a novel

68 ing epidermal turn-over rate, and protecting HCKs against stress.

69 tophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new t

70 n vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with r

71 is is only inducible in IL-1alpha-stimulated HCKs.

72 SYK, as well as the MYD88-downstream target HCK.

73 dings highlight the feasibility of targeting HCK, a key driver of mutated MYD88 pro-survival signalin

74 (HCK) transcription and activation, and that HCK is activated by interleukin 6 (IL-6).

75 Docking and pull-down studies confirmed that HCK was a target of ibrutinib.

76 ic inhibition of HCK activity indicated that HCK is required for HCMV reactivation.

77 nd single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory ma

78 face between NLRP12 and HCK, suggesting that HCK likely binds NLRP12 in the region between its NACHT

79 The findings support that HCK expression and activation is triggered by mutated MY

80 Furthermore, the HCK/SFK activity was linked to recruitment of the monocy

81 on tyrosine residues in the presence of the HCK p59 or FGR.

82 so blocked adenosine triphosphate binding to HCK, whereas transduction of mutated MYD88 expressing WM

83 ed on the crystal structures of PP1 bound to HCK and N(6)-(benzyl)-ADP bound to c-Src (T338G).

84 Over-expression of mutated MYD88 triggers HCK and IL-6 transcription, whereas knockdown of HCK red

85 ctivated the TGF-beta/Smad3 pathway, whereas HCK knockdown inhibited it.