Molecule Information

General Information of the Molecule (ID: Mol02033)

• Name: Tyrosine-protein kinase Yes (YES) ,Canis lupus
• Synonyms: YES1; YES
• Molecule Type: Protein
• Gene Name: YES
• Sequence:
  MGCIKSKEDKGPAIKYRNTPEPVSVSHYGAEPTQATPWPSSSGWGTAFNFSSLSMTGFGG
  SSGVTPFGGASSSFSVVPSPYPAGLTGGVTIFVALYDYEARTTEDLSFKGGERFQIINNT
  EGDWWEARSIATGKNGYIPSNYVAPADSIAAEEWYFGKMGRKDAERLLLNPGNQRGIFLV
  RESETTKGAYSLSIRDWDEIRGDNVKHYKIRKLDNGGYYITTRAQFDTLQKLVKHSTEHA
  DGLCHKLTTVCPTVKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTKVAI
  KTLKLGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMSKGSLLDFLKEGD
  GKYLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGENLVCKIADFGLARLIEDN
  EYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILQTELTTKGRVPYPGMVNREVLEQ
  VERGYRMPCPQGCPESLHELMNLCWKKDPDERPTFEYIQSFLEDYFTAAEPQYQPGENL
• Function: Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis (By similarity).
• Uniprot ID: YES_CANLF

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Carnivora
Family: Canidae
Genus: Canis
Species: Canis lupus

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Vascular sarcoma [1]

• Resistant Disease: Vascular sarcoma [ICD-11: 2C35.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: COSB cells; Nasopharynx; Canis lupus familiaris (Dog) (Canis familiaris); CVCL_5I33
• In Vitro Model: DD-1 cells; Synovium; Canis lupus familiaris (Dog); CVCL_0C94
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: For this study, we demonstrate that both hemangiosarcoma and angiosarcoma cells with high expression of CSF-1R are more drug resistant than their CSF-1R low-expressing counterparts, indicating a shared mechanism for the observed treatment failures and subsequent drug resistance. Our data also suggest that part of this resistance may be achieved through drug sequestration within cellular lysosomes.

Disease Class: Vascular sarcoma [1]

• Resistant Disease: Vascular sarcoma [ICD-11: 2C35.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: AS5 cells; Blood vessel; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: For this study, we demonstrate that both hemangiosarcoma and angiosarcoma cells with high expression of CSF-1R are more drug resistant than their CSF-1R low-expressing counterparts, indicating a shared mechanism for the observed treatment failures and subsequent drug resistance. Our data also suggest that part of this resistance may be achieved through drug sequestration within cellular lysosomes.

References

• Ref 1: Lysosomal drug sequestration as a mechanism of drug resistance in vascular sarcoma cells marked by high CSF-1R expression .Vasc Cell. 2014 Oct 1;6:20. doi: 10.1186/2045-824X-6-20. eCollection 2014. 10.1186/2045-824X-6-20