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Search results for: ACK1 Antibody

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#22952966   2012/08/30 To Up

Cortactin is a substrate of activated Cdc42-associated kinase 1 (ACK1) during ligand-induced epidermal growth factor receptor downregulation.

Epidermal growth factor receptor (EGFR) internalization following ligand binding controls EGFR downstream pathway signaling activity. Internalized EGFR is poly-ubiquitinated by Cbl to promote lysosome-mediated degradation and signal downregulation. ACK1 is a non-receptor tyrosine kinase that interacts with ubiquitinated EGFR to facilitate EGFR degradation. Dynamic reorganization of the cortical actin cytoskeleton controlled by the actin related protein (Arp)2/3 complex is important in regulating EGFR endocytosis and vesicle trafficking. How ACK1-mediated EGFR internalization cooperates with Arp2/3-based actin dynamics during EGFR downregulation is unclear.
Laura C Kelley, Scott A Weed

2577 related Products with: Cortactin is a substrate of activated Cdc42-associated kinase 1 (ACK1) during ligand-induced epidermal growth factor receptor downregulation.

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#20979614   2010/10/27 To Up

Regulation of Ack1 localization and activity by the amino-terminal SAM domain.

The mechanisms that regulate the activity of the nonreceptor tyrosine kinase Ack1 (activated Cdc42-associated kinase) are poorly understood. The amino-terminal region of Ack1 is predicted to contain a sterile alpha motif (SAM) domain. SAM domains share a common fold and mediate protein-protein interactions in a wide variety of proteins. Here, we addressed the importance of the Ack1 SAM domain in kinase activity.
Victoria Prieto-Echagüe, Azad Gucwa, Deborah A Brown, W Todd Miller

2016 related Products with: Regulation of Ack1 localization and activity by the amino-terminal SAM domain.

96 samples100 ug0.02ml100μg100μg100μg192 samples100 ug96T0.05mg100μg

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#20623637   // To Up

Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity.

Androgen receptor (AR) plays a critical role in the progression of both androgen-dependent and androgen-independent prostate cancer (AIPC). Ligand-independent activation of AR in AIPC or castration resistant prostate cancer (CRPC) is often associated with poor prognosis. Recently, tyrosine kinase Ack1 has been shown to regulate AR activity by phosphorylating it at tyrosine 267 and this event was shown to be critical for AIPC growth. However, whether a small molecule inhibitor that can mitigate Ack1 activation is sufficient to abrogate AR activity on AR regulated promoters in androgen-depleted environment is not known.
Kiran Mahajan, Sridevi Challa, Domenico Coppola, Harshani Lawrence, Yunting Luo, Harsukh Gevariya, Weiwei Zhu, Y Ann Chen, Nicholas J Lawrence, Nupam P Mahajan

2620 related Products with: Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity.

8 inhibitors0.1ml96T5 inhibitors400Tests5mg200ul100ul7 inhibitors96T200ug1000

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#20383201   2010/04/12 To Up

Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases.

Activation of androgen receptor (AR) may have a role in the development of castration-resistant prostate cancer. Two intracellular tyrosine kinases, Ack1 (activated cdc42-associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. However, the upstream signals that activate these kinases and lead to AR activation are incompletely characterized. In this study, we investigated AR phosphorylation in response to non-androgen ligand stimulation using phospho-specific antibodies. Treatment of LNCaP and LAPC-4 cells with epidermal growth factor (EGF), heregulin, Gas6 (ligand binding to the Mer receptor tyrosine kinase and activating Ack1 downstream), interleukin (IL)-6 or bombesin stimulated cell proliferation in the absence of androgen. Treatment of LNCaP and LAPC-4 cells with EGF, heregulin or Gas6 induced AR phosphorylation at Tyr-267, whereas IL-6 or bombesin treatment did not. AR phosphorylation at Tyr-534 was induced by treatment with EGF, IL-6 or bombesin, but not by heregulin or Gas6. Small interfering RNA-mediated knockdown of Ack1 or Src showed that Ack1 mediates heregulin- and Gas6-induced AR Tyr-267 phosphorylation, whereas Src mediates Tyr-534 phosphorylation induced by EGF, IL-6 and bombesin. Dasatinib, a Src inhibitor, blocked EGF-induced Tyr-534 phosphorylation. In addition, we showed that dasatinib also inhibited Ack1 kinase. Dasatinib inhibited heregulin-induced Ack1 kinase activity and AR Tyr-267 phosphorylation. In addition, dasatinib inhibited heregulin-induced AR-dependent reporter activity. Dasatinib also inhibited heregulin-induced expression of endogenous AR target genes. Dasatinib inhibited Ack1-dependent colony formation and prostate xenograft tumor growth in castrated mice. Interestingly, Ack1 or Src knockdown or dasatinib did not inhibit EGF-induced AR Tyr-267 phosphorylation or EGF-stimulated AR activity, suggesting the existence of an additional tyrosine kinase that phosphorylates AR at Tyr-267. These data suggest that specific tyrosine kinases phosphorylate AR at distinct sites and that dasatinib may exert antitumor activity in prostate cancer through inhibition of Ack1.
Y Liu, M Karaca, Z Zhang, D Gioeli, H S Earp, Y E Whang

2039 related Products with: Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases.

200ug50 ug 100ug100.00 ul1 ml100ul2 Pieces/Box50 ug 100ug2 Pieces/Box100ug100ul

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#20110370   2010/01/28 To Up

Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1.

Ack1 is a nonreceptor tyrosine kinase that participates in tumorigenesis, cell survival, and migration. Relatively little is known about the mechanisms that regulate Ack1 activity. Recently, four somatic missense mutations of Ack1 were identified in cancer tissue samples, but the effects on Ack1 activity, and function have not been described. These mutations occur in the N-terminal region, the C-lobe of the kinase domain, and the SH3 domain. Here, we show that the cancer-associated mutations increase Ack1 autophosphorylation in mammalian cells without affecting localization and increase Ack1 activity in immune complex kinase assays. The cancer-associated mutations potentiate the ability of Ack1 to promote proliferation and migration, suggesting that point mutation is a mechanism for Ack1 deregulation. We propose that the C-terminal Mig6 homology region (MHR) (residues 802-990) participates in inhibitory intramolecular interactions. The isolated kinase domain of Ack1 interacts directly with the MHR, and the cancer-associated E346K mutation prevents binding. Likewise, mutation of a key hydrophobic residue in the MHR (Phe(820)) prevents the MHR-kinase interaction, activates Ack1, and increases cell migration. Thus, the cancer-associated mutation E346K appears to destabilize an autoinhibited conformation of Ack1, leading to constitutively high Ack1 activity.
Victoria Prieto-Echagüe, Azad Gucwa, Barbara P Craddock, Deborah A Brown, W Todd Miller

1628 related Products with: Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1.

100 100ul100ul100 ul96T2 Pieces/Box100 8 inhibitors100 5 96T

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#17592719   2007/05/10 To Up

An ultrasensitive high-throughput electrochemiluminescence immunoassay for the Cdc42-associated protein tyrosine kinase ACK1.

Several drugs inhibiting protein kinases have been launched successfully, demonstrating the attractiveness of protein kinases as therapeutic targets. Functional genomics research within both academia and industry has led to the identification of many more kinases as potential drug targets. Although a number of well-known formats are used for measuring protein kinase activity, some less well-characterized protein kinases identified through functional genomics present particular challenges for existing assay formats when there is limited knowledge of the endogenous substrates or activation mechanisms for these novel kinase targets. This is especially the case when a very sensitive assay is required to differentiate often highly potent inhibitors developed by late-stage medicinal chemistry programs. ACK1 is a non-receptor tyrosine kinase that has been shown to be involved in tumorigenesis and metastasis. Here we describe the development of an extremely sensitive high-throughput assay for ACK1 capable of detecting 240 fmol per well of the kinase reaction product employing a BV-tag-based electrochemiluminescence assay. This assay is universally applicable to protein tyrosine kinases using a BV-tag-labeled monoclonal antibody against phosphotyrosine. Furthermore, this assay can be extended to the evaluation of Ser/Thr kinases in those cases where an antibody recognizing the phospho-product is available.
Shou-Hua Xiao, Ellyn Farrelly, John Anzola, Daniel Crawford, Xianyun Jiao, Jinqian Liu, Merrill Ayres, Shyun Li, Linda Huang, Rajiv Sharma, Frank Kayser, Holger Wesche, Stephen W Young

1277 related Products with: An ultrasensitive high-throughput electrochemiluminescence immunoassay for the Cdc42-associated protein tyrosine kinase ACK1.

100ug100ug100ug100 100 100μg100ug100 μg0.1ml100ug100ul100 μg

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#9209099   // To Up

Expression and function of the c-kit proto-oncogene protein in mouse sperm.

The presence and role of the c-kit protein were examined in mature sperm of the mouse. Monoclonal antibodies (mAbs) against the c-kit protein were used to perform immunohistochemical staining, electron microscopy studies, and Western blot analysis. The acrosomal region of both fixed and unfixed noncapacitated sperm stained with the antibodies. No acrosomal staining was noted in acrosome-reacted (AR) sperm. Electron microscopy studies demonstrated immunogold label on the plasma membrane of the acrosome and confirmed the lack of binding following the acrosome reaction. Proteins corresponding to 33 kDa, 48 kDa, and 150 kDa were detected by the antibodies utilizing Western blot analysis. The 48-kDa and 150-kDa proteins were released into the media during sperm capacitation, and release from the acrosome was dependent upon the acrosome reaction. The mAbs significantly inhibited the acrosome reaction and increased sperm agglutination. Monoclonal antibody ACK1 significantly inhibited the motility of the sperm, whereas mAbs ACK2 and NCL-ckit did not. These results suggest that c-kit-related proteins are present in mature sperm and may play a role in capacitation and/or the acrosome reaction.
H Feng, J I Sandlow, A Sandra

2683 related Products with: Expression and function of the c-kit proto-oncogene protein in mouse sperm.

100ug Lyophilized0.1mg100.00 ug5ug1mg5ug100.00 ug1 Set100ug Lyophilized100.2 mg2ug

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