Faculty Opinions recommendation of Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules.

2021 ◽  
Author(s):  
Ron Prywes
Keyword(s):  
Ras Signaling ◽  
Cytoplasmic Protein ◽  
Protein Granules

scholarly journals Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules

Cell ◽  
2021 ◽  
Author(s):  
Asmin Tulpule ◽  
Juan Guan ◽  
Dana S. Neel ◽  
Hannah R. Allegakoen ◽  
Yone Phar Lin ◽  
...  
Keyword(s):  
Ras Signaling ◽  
Cytoplasmic Protein ◽  
Protein Granules

scholarly journals Kinase-Mediated RAS Signaling Via Membraneless Cytoplasmic Protein Granules

2020 ◽  
Author(s):  
Asmin Tulpule ◽  
Juan Guan ◽  
Dana Neel ◽  
Yone Phar Lin ◽  
Ann Heslin ◽  
...  
Keyword(s):  
Ras Signaling ◽  
Cytoplasmic Protein ◽  
Protein Granules

scholarly journals Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules

2019 ◽  
Author(s):  
Asmin Tulpule ◽  
Juan Guan ◽  
Dana S. Neel ◽  
Yone Phar Lin ◽  
Ann Heslin ◽  
...  
Keyword(s):  
Lipid Membrane ◽  
De Novo ◽  
Protein Assembly ◽  
Mapk Signaling ◽  
Higher Order ◽  
Ras Signaling ◽  
List Type ◽  
Cytoplasmic Protein ◽  
Independent Manner ◽  
Protein Granules

SummaryReceptor tyrosine kinase (RTK)-mediated activation of downstream effector pathways such as the RAS GTPase/MAP kinase (MAPK) signaling cascade is thought to occur exclusively from lipid membrane compartments in mammalian cells. Here, we uncover a membraneless, protein granule-based subcellular structure that can organize RTK/RAS/MAPK signaling in cancer. Chimeric (fusion) oncoproteins involving certain RTKs including ALK and RET undergo de novo higher-order assembly into membraneless cytoplasmic protein granules. These pathogenic biomolecular condensates locally concentrate the RAS activating complex GRB2/SOS1 and activate RAS in a lipid membrane-independent manner to initiate MAPK signaling. Formation of membraneless protein granules by RTK oncoproteins is both necessary and sufficient for RAS/MAPK signaling output in cells. Our findings reveal membraneless, higher-order cytoplasmic protein assembly as a distinct subcellular platform to activate RTKs and RAS GTPases and a general principle by which cells can organize oncogenic signaling.HighlightsRTK oncoproteins can form de novo membraneless cytoplasmic protein granulesRTK protein granules activate RAS in lipid membrane-independent mannerHigher-order protein assembly is critical for oncogenic RAS/MAPK signalingProtein granules are a distinct subcellular platform for organizing RTK signaling

scholarly journals Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS.

1995 ◽  
Vol 15 (2) ◽  
pp. 835-842 ◽  
Author(s):  
Y Maru ◽  
K L Peters ◽  
D E Afar ◽  
M Shibuya ◽  
O N Witte ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Sh2 Domain ◽  
Binding Domain ◽  
Ras Signaling ◽  
Cytoplasmic Protein ◽  
Nucleotide Exchange ◽  
Protein Tyrosine

The human bcr gene encodes a protein with serine/threonine kinase activity, CDC24/dbl homology, a GAP domain, and an SH2-binding region. However, the precise physiological functions of BCR are unknown. Coexpression of BCR with the cytoplasmic protein-tyrosine kinase encoded by the c-fes proto-oncogene in Sf-9 cells resulted in stable BCR-FES protein complex formation and tyrosine phosphorylation of BCR. Association involves the SH2 domain of FES and a novel binding domain localized to the first 347 amino acids of the FES N-terminal region. Deletion of the homologous N-terminal BCR-binding domain from v-fps, a fes-related transforming oncogene, abolished transforming activity and tyrosine phosphorylation of BCR in vivo. Tyrosine phosphorylation of BCR in v-fps-transformed cells induced its association with GRB-2/SOS, the RAS guanine nucleotide exchange factor complex. These data provide evidence that BCR couples the cytoplasmic protein-tyrosine kinase and RAS signaling pathways.

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