scholarly journals Hematopoietic cell kinase enhances osteosarcoma development via the MEK/ERK pathway

2021 ◽  
Author(s):  
Weibo Liu ◽  
Teng Li ◽  
Wenhao Hu ◽  
Quanbo Ji ◽  
Fanqi Hu ◽  
...  
Keyword(s):  
Hematopoietic Cell ◽  
Erk Pathway ◽  
Hematopoietic Cell Kinase

scholarly journals Inhibition of hematopoietic cell kinase dysregulates microglial function and accelerates early stage Alzheimer's disease-like neuropathology

Glia ◽  
2018 ◽  
Vol 66 (12) ◽  
pp. 2700-2718 ◽  
Author(s):  
Siok Lam Lim ◽  
Diana Nguyen Tran ◽  
Joannee Zumkehr ◽  
Christine Chen ◽  
Sagar Ghiaar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Hematopoietic Cell ◽  
Hematopoietic Cell Kinase

Suppression of hematopoietic cell kinase ameliorates the bone destruction associated with inflammation

2019 ◽  
Vol 30 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Yusoon Kim ◽  
Mikihito Hayashi ◽  
Takehito Ono ◽  
Tetsuya Yoda ◽  
Hiroshi Takayanagi ◽  
...  
Keyword(s):  
Bone Destruction ◽  
Hematopoietic Cell ◽  
Hematopoietic Cell Kinase

scholarly journals Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer’s Disease–Like Neuropathology in Tg2576 Mice

2020 ◽  
Vol 57 (5) ◽  
pp. 2447-2460 ◽  
Author(s):  
Siok Lam Lim ◽  
Diana Nguyen Tran ◽  
Zanett Kieu ◽  
Christine Chen ◽  
Emmanuel Villanueva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hematopoietic Cell ◽  
Genetic Ablation ◽  
Hematopoietic Cell Kinase ◽  
Tg2576 Mice

HIV-1 Nef Alleles Show Differential Activation of Hematopoietic Cell Kinase in a Yeast Model System.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3107-3107
Author(s):  
Ronald P. Trible ◽  
Thomas E. Smithgall
Keyword(s):  
Growth Inhibition ◽  
Mammalian Cells ◽  
Sh2 Domain ◽  
Model System ◽  
Hematopoietic Cell ◽  
Yeast Growth ◽  
High Affinity ◽  
Hematopoietic Cell Kinase ◽  
Aids Progression ◽  
Hiv 1

Abstract Hematopoietic cell kinase (Hck) is a member of the Src family of non-receptor protein-tyrosine kinases that is expressed strongly in macrophages, an important target cell type for human immunodeficiency virus (HIV). The HIV Nef protein, a critical AIDS progression factor, binds Hck with unusually high affinity and induces Hck activation. Nef-mediated Hck activation has been proposed to trigger signaling pathways important for the establishment of HIV infection and subsequent progression to AIDS. Previous studies have utilized sequence alignments and binding assays to predict the functionality of Hck-Nef interactions, but these studies do not directly investigate the ability of Nef alleles to activate Hck. To better address this issue, we have created a model system in Saccharomyces cerevisiae based on previous findings that ectopic expression of c-Src arrests yeast growth in a kinase-dependent fashion. To establish the utility of this system for Hck and Nef, we first created a Hck variant containing a C-terminal sequence modified to encode the high-affinity SH2-domain binding sequence Tyr-Glu-Glu-Ile (HckYEEI). This modified sequence allows for autophosphorylation of the new tail and the subsequent intramolecular binding to the Hck SH2 domain. The resulting HckYEEI molecule models the physiologically down-regulated (inactive) form of Hck in structure and function. Unlike wild-type Hck, HckYEEI showed little kinase activity and failed to induce growth suppression in yeast. Importantly, co-expression with the Nef-SF2 allele activated HckYEEI, resulting in growth arrest. This effect was dependent on the conserved Nef proline-rich motif essential for Hck binding through its SH3 domain. However, Nef-SF2 did not activate FynYEEI, consistent with our previous data that the Fyn tyrosine kinase is not activated by Nef in mammalian cells. We then tested several additional laboratory HIV-1 Nef alleles for their ability to activate HckYEEI. Consensus, Lai, NL4.3, SF2, and YU-2 Nef alleles activated HckYEEI to varying degrees, as reflected by yeast growth inhibition. In contrast, Nef-Eli failed to suppress growth in the presence of HckYEEI, consistent with its inability to bind the Hck SH3 domain in vitro. Growth inhibition paralleled tyrosine phosphorylation of yeast proteins on anti-phosphotyrosine immunoblots. The differential effects of these Nef alleles on Hck activation correlated closely with previous results in mammalian cells. Taken together, these studies validate the use of yeast to reconstitute Nef-Hck interactions in a system amenable to screens of clinical Nef isolates, which may have predictive value in terms of AIDS progression.

scholarly journals The SH3 regulatory domain of the hematopoietic cell kinase Hck binds ELMO via its polyproline motif

FEBS Open Bio ◽  
2015 ◽  
Vol 5 (1) ◽  
pp. 99-106 ◽  
Author(s):  
Rida Awad ◽  
Marion Sévajol ◽  
Isabel Ayala ◽  
Anne Chouquet ◽  
Philippe Frachet ◽  
...  
Keyword(s):  
Hematopoietic Cell ◽  
Regulatory Domain ◽  
Hematopoietic Cell Kinase ◽  
Polyproline Motif
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