Kinase-deficient BTK mutants confer ibrutinib resistance through activation of the kinase HCK
Sci Signal. 2022 May 31;15(736):eabg5216. doi: 10.1126/scisignal.abg5216. Epub 2022 May 31.ABSTRACTThe Bruton's tyrosine kinase (BTK) inhibitor ibrutinib irreversibly binds BTK at Cys481, inhibiting its kinase activity and thus blocking transduction of B cell receptor (BCR) signaling. Although ibrutinib is durably effective in patients with B cell malignancies, many patients still develop ibrutinib-resistant disease. Resistance can arise because of mutations at the ibrutinib-binding site in BTK. Here, we characterized the mechanism by which two BTK mutations, C481F and C481Y, may lead to ibrutinib resistance. Both mutants ...
Source: Science Signaling - May 31, 2022 Category: Biomedical Science Authors: Kamaldeep Dhami Anirban Chakraborty Tarikere L Gururaja Leo W-K Cheung Chaohong Sun Felix DeAnda XiaoDong Huang Source Type: research

The perception and response of T cells to a changing environment are based on the law of initial value
Sci Signal. 2022 May 31;15(736):eabj9842. doi: 10.1126/scisignal.abj9842. Epub 2022 May 31.ABSTRACTαβ T cells are critical components of the adaptive immune system and are capable of inducing sterilizing immunity after pathogen infection and eliminating transformed tumor cells. The development and function of T cells are controlled through the T cell antigen receptor, which recognizes peptides displayed on major histocompatibility complex (MHC) molecules. Here, we review how T cells generate the ability to recognize self-peptide-bound MHC molecules and use signals derived from these interactions to instruct cellular deve...
Source: Science Signaling - May 31, 2022 Category: Biomedical Science Authors: Eric S Huseby Emma Teixeiro Source Type: research

Formate for tumor progression
Sci Signal. 2022 May 31;15(736):eadd1844. doi: 10.1126/scisignal.add1844. Epub 2022 May 31.ABSTRACTA bacterial metabolite promotes the progression of colorectal cancer.PMID:35639857 | DOI:10.1126/scisignal.add1844 (Source: Science Signaling)
Source: Science Signaling - May 31, 2022 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research

Kinase-deficient BTK mutants confer ibrutinib resistance through activation of the kinase HCK
Sci Signal. 2022 May 31;15(736):eabg5216. doi: 10.1126/scisignal.abg5216. Epub 2022 May 31.ABSTRACTThe Bruton's tyrosine kinase (BTK) inhibitor ibrutinib irreversibly binds BTK at Cys481, inhibiting its kinase activity and thus blocking transduction of B cell receptor (BCR) signaling. Although ibrutinib is durably effective in patients with B cell malignancies, many patients still develop ibrutinib-resistant disease. Resistance can arise because of mutations at the ibrutinib-binding site in BTK. Here, we characterized the mechanism by which two BTK mutations, C481F and C481Y, may lead to ibrutinib resistance. Both mutants ...
Source: Science Signaling - May 31, 2022 Category: Biomedical Science Authors: Kamaldeep Dhami Anirban Chakraborty Tarikere L Gururaja Leo W-K Cheung Chaohong Sun Felix DeAnda XiaoDong Huang Source Type: research

The perception and response of T cells to a changing environment are based on the law of initial value
Sci Signal. 2022 May 31;15(736):eabj9842. doi: 10.1126/scisignal.abj9842. Epub 2022 May 31.ABSTRACTαβ T cells are critical components of the adaptive immune system and are capable of inducing sterilizing immunity after pathogen infection and eliminating transformed tumor cells. The development and function of T cells are controlled through the T cell antigen receptor, which recognizes peptides displayed on major histocompatibility complex (MHC) molecules. Here, we review how T cells generate the ability to recognize self-peptide-bound MHC molecules and use signals derived from these interactions to instruct cellular deve...
Source: Science Signaling - May 31, 2022 Category: Biomedical Science Authors: Eric S Huseby Emma Teixeiro Source Type: research

Formate for tumor progression
Sci Signal. 2022 May 31;15(736):eadd1844. doi: 10.1126/scisignal.add1844. Epub 2022 May 31.ABSTRACTA bacterial metabolite promotes the progression of colorectal cancer.PMID:35639857 | DOI:10.1126/scisignal.add1844 (Source: Science Signaling)
Source: Science Signaling - May 31, 2022 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research

A twist in β-arrestin's tail
Sci Signal. 2022 May 24;15(735):eadd1034. doi: 10.1126/scisignal.add1034. Epub 2022 May 24.ABSTRACTBoth agonist binding and phosphorylation of the receptor C-tail are required for a GPCR to recruit and activate β-arrestins.PMID:35609126 | DOI:10.1126/scisignal.add1034 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

The lncRNA PILA promotes NF- κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1
This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.PMID:35609127 | DOI:10.1126/scisignal.abm6265 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: Su'an Tang Yumei Cao Zhaopeng Cai Xiaoyu Nie Jianzhao Ruan Zuoqing Zhou Guangfeng Ruan Zhaohua Zhu Weiyu Han Changhai Ding Source Type: research

A twist in β-arrestin's tail
Sci Signal. 2022 May 24;15(735):eadd1034. doi: 10.1126/scisignal.add1034. Epub 2022 May 24.ABSTRACTBoth agonist binding and phosphorylation of the receptor C-tail are required for a GPCR to recruit and activate β-arrestins.PMID:35609126 | DOI:10.1126/scisignal.add1034 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

The lncRNA PILA promotes NF- κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1
This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.PMID:35609127 | DOI:10.1126/scisignal.abm6265 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: Su'an Tang Yumei Cao Zhaopeng Cai Xiaoyu Nie Jianzhao Ruan Zuoqing Zhou Guangfeng Ruan Zhaohua Zhu Weiyu Han Changhai Ding Source Type: research

A twist in β-arrestin's tail
Sci Signal. 2022 May 24;15(735):eadd1034. doi: 10.1126/scisignal.add1034. Epub 2022 May 24.ABSTRACTBoth agonist binding and phosphorylation of the receptor C-tail are required for a GPCR to recruit and activate β-arrestins.PMID:35609126 | DOI:10.1126/scisignal.add1034 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

The lncRNA PILA promotes NF- κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1
This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.PMID:35609127 | DOI:10.1126/scisignal.abm6265 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: Su'an Tang Yumei Cao Zhaopeng Cai Xiaoyu Nie Jianzhao Ruan Zuoqing Zhou Guangfeng Ruan Zhaohua Zhu Weiyu Han Changhai Ding Source Type: research

A twist in β-arrestin's tail
Sci Signal. 2022 May 24;15(735):eadd1034. doi: 10.1126/scisignal.add1034. Epub 2022 May 24.ABSTRACTBoth agonist binding and phosphorylation of the receptor C-tail are required for a GPCR to recruit and activate β-arrestins.PMID:35609126 | DOI:10.1126/scisignal.add1034 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

The lncRNA PILA promotes NF- κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1
This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.PMID:35609127 | DOI:10.1126/scisignal.abm6265 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: Su'an Tang Yumei Cao Zhaopeng Cai Xiaoyu Nie Jianzhao Ruan Zuoqing Zhou Guangfeng Ruan Zhaohua Zhu Weiyu Han Changhai Ding Source Type: research

A twist in β-arrestin's tail
Sci Signal. 2022 May 24;15(735):eadd1034. doi: 10.1126/scisignal.add1034. Epub 2022 May 24.ABSTRACTBoth agonist binding and phosphorylation of the receptor C-tail are required for a GPCR to recruit and activate β-arrestins.PMID:35609126 | DOI:10.1126/scisignal.add1034 (Source: Science Signaling)
Source: Science Signaling - May 24, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research