Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A.
CD44 has been postulated as a cell surface coreceptor for augmenting receptor tyrosine kinase (RTK) signaling. However, how exactly CD44 triggers RTK-dependent signaling remained largely unclear. Here we report an unexpected mechanism by which the CD44s splice isoform is internalized into endosomes to attenuate EGFR degradation. We identify a CD44s-interacting small GTPase, Rab7A, and show that CD44s inhibits Rab7A-mediated EGFR trafficking to lysosomes and subsequent degradation. Importantly, CD44s levels correlate with EGFR signature and predict poor prognosis in glioblastomas. Because Rab7A facilitates trafficking of many RTKs to lysosomes, our findings identify CD44s as a Rab7A regulator to attenuate RTK degradation.
['Wang|Wei|W|', 'Zhang|Honghong|H|', 'Liu|Sali|S|', 'Kim|Chung Kwon|CK|', 'Xu|Yilin|Y|', 'Hurley|Lisa A|LA|', 'Nishikawa|Ryo|R|', 'Nagane|Motoo|M|', 'Hu|Bo|B|', 'Stegh|Alexander H|AH|', 'Cheng|Shi-Yuan|SY|', 'Cheng|Chonghui|C|']
D002460:Cell Line D011992:Endosomes D066246:ErbB Receptors D005909:Glioblastoma D057809:HEK293 Cells D006801:Humans D018960:Hyaluronan Receptors D008247:Lysosomes D020033:Protein Isoforms D021381:Protein Transport D015398:Signal Transduction D020691:rab GTP-Binding Proteins D000090802:rab7 GTP-Binding Proteins
CD44s splice isoform EGFR Rab7A GBM