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Last update 23 Jan 2025

CRK

Last update 23 Jan 2025

Basic Info

Synonyms

Adapter molecule crk, CRK, CRK proto-oncogene, adaptor protein

+ [2]

Introduction

Regulates cell adhesion, spreading and migration (PubMed:31311869). Mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4 (PubMed:19004829). May regulate the EFNA5-EPHA3 signaling (By similarity). Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1.

Drugs associated with CRK

RGB-286147

Target

CRK

Mechanism

CRK inhibitors

Active Org.

ThinkMolecular Technologies Pvt. Ltd

Originator Org.

ThinkMolecular Technologies Pvt. Ltd

Active Indication-

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CRK

100 Translational Medicine associated with CRK

0 Patents (Medical) associated with CRK

953

Literatures (Medical) associated with CRK

01 Jan 2025·Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

Identification of dystrophin Dp71dΔ71-associated proteins in PC12 cells by quantitative proteomics

Article

Author: Ríos-Castro, Emmanuel ; Azotla-Vilchis, Coztli ; Aragón, Jorge ; Ceja, Víctor ; Merino-Jiménez, Candelaria ; Montanez, Cecilia

Dystrophin Dp71 is essential for the development of the nervous system. Its alteration is associated with intellectual disability. Different Dp71 isoforms are generated by alternative splicing; however, their functions have not been fully described. Here, we identified Dp71d_Δ71-associated proteins to understand the complex functions. PC12 cells, stably transfected with pTRE2pur-Myc/Dp71d_Δ71 or pTRE2pur-Myc empty vector (EV), were analyzed by immunoprecipitation followed with quantitative proteomics with data-independent acquisition and ion mobility separation. We used the Top3 method to quantify absolutely every protein detected. A total of 106 proteins were quantified with Progenesis QI software and the database UP000002494. Seven new proteins associated with Dp71d_Δ71 were selected with at least 2-fold quantity between immunoprecipitated proteins of PC12-Myc/Dp71d_Δ71 versus PC12-EV cells. These results revealed new proteins that interact with Dp71d_Δ71, including β-Tubulin, S-adenosylmethionine synthase isoform type-2, adapter molecule crk, helicase with zinc finger 2, WD repeat domain 93, cyclin-L2 and myosin-10, which are related to cell migration and/or cell growth. The results lay the foundation for future research on the relationship between these proteins and Dp71 isoforms.

31 Dec 2024·Virulence

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality

Article

Author: Li, Ze ; Xu, Qiu-Yan ; Liu, Dan ; Yi, Dong-Yu ; Zheng, Xin-Qi ; Meng, Qing-Qi ; Tong, Man-Li ; Yang, Tian-Ci ; Ye, Wei-Ming

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

01 Dec 2024·Molecular Biology Reports

Development and tissue specific expression of RAPGEF1 (C3G) transcripts having exons encoding disordered segments with predicted regulatory function

Article

Author: Goel, Abhishek ; Verma, Archana ; Koner, Niladri ; Radha, Vegesna ; Gunasekaran, Gowthaman

BACKGROUNDThe ubiquitously expressed Guanine nucleotide exchange factor, RAPGEF1 (C3G), is essential for early development of mouse embryos. It functions to regulate gene expression and cytoskeletal reorganization, thereby controlling cell proliferation and differentiation. While multiple transcripts have been predicted, their expression in mouse tissues has not been investigated in detail.METHODS & RESULTSFull length RAPGEF1 isoforms primarily arise due to splicing at two hotspots, one involving exon-3, and the other involving exons 12-14 incorporating amino acids immediately following the Crk binding region of the protein. These isoforms vary in expression across embryonic and adult organs. We detected the presence of unannotated, and unpredicted transcripts with incorporation of cassette exons in various combinations, specifically in the heart, brain, testis and skeletal muscle. Isoform switching was detected as myocytes in culture and mouse embryonic stem cells were differentiated to form myotubes, and embryoid bodies respectively. The cassette exons encode a serine-rich polypeptide chain, which is intrinsically disordered, and undergoes phosphorylation. In silico structural analysis using AlphaFold indicated that the presence of cassette exons alters intra-molecular interactions, important for regulating catalytic activity. LZerD based docking studies predicted that the isoforms with one or more cassette exons differ in interaction with their target GTPase, RAP1A.CONCLUSIONSOur results demonstrate the expression of novel RAPGEF1 isoforms, and predict cassette exon inclusion as an additional means of regulating RAPGEF1 activity in various tissues and during differentiation.

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