Inhibitory effect of SPE-39 due to tyrosine phosphorylation and ubiquitination on the function of Vps33B in the EGF-stimulated cells.
Although SPE-39 is a binding protein to Vps33B that is one of the subunit in the mammalian HOPS complex, the elements of SPE-39 function remain unknown. Here, we show that tyrosine phosphorylation of SPE-39 following EGF stimulation plays a role in the stability of SPE-39 itself. Ubiquitination of the C-terminal region of SPE-39 was also elevated in response to EGF stimulation, and this process was regulated by the phosphorylation of Tyr-11 in SPE-39. However, association of Vps33B with SPE-39 inhibited the elevation of ubiquitination of SPE-39 following EGF stimulation, which might be responsible for the stabilization of SPE-39. Furthermore, an opposing functional relationship between SPE-39 and Vps33B on the downregulation of the EGF receptor was observed in EGF-stimulated COS-7 cells.
Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan.
Ayumi
A
Ishii
Kanae
K
Kamimori
Mineyoshi
M
Hiyoshi
Hiroshi
H
Kido
Takeshi
T
Ohta
Hiroaki
H
Konishi
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry*; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods; D010766:Phosphorylation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry*; D033921:Vesicular Transport Proteins / Q000737:chemistry*
D002352:Carrier Proteins; D018076:DNA, Complementary; D025801:Ubiquitin; C539711:VIPAS39 protein, human; C411584:VPS33B protein, human; D033921:Vesicular Transport Proteins; D014443:Tyrosine; D004815:Epidermal Growth Factor