Phospholipase C-gamma1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis.
Phospholipase C-gamma1 (PLC-gamma1), which interacts with a variety of signaling molecules through its two Src homology (SH) 2 domains and a single SH3 domain has been implicated in the regulation of many cellular functions. We demonstrate that PLC-gamma1 acts as a guanine nucleotide exchange factor (GEF) of dynamin-1, a 100 kDa GTPase protein, which is involved in clathrin-mediated endocytosis of epidermal growth factor (EGF) receptor. Overexpression of PLC-gamma1 increases endocytosis of the EGF receptor by increasing guanine nucleotide exchange activity of dynamin-1. The GEF activity of PLC-gamma1 is mediated by the direct interaction of its SH3 domain with dynamin-1. EGF-dependent activation of ERK and serum response element (SRE) are both up-regulated in PC12 cells stably overexpressing PLC-gamma1, but knockdown of PLC-gamma1 by siRNA significantly reduces ERK activation. These results establish a new role for PLC-gamma1 in the regulation of endocytosis and suggest that endocytosis of activated EGF receptors may mediate PLC-gamma1-dependent proliferation.
Choi
Jang Hyun
JH
Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyojadong, Pohang, Kyungbuk 790-784, Republic of Korea.
Park
Jong Bae
JB
Bae
Sun Sik
SS
Yun
Sanguk
S
Kim
Hyeon Soo
HS
Hong
Won-Pyo
WP
Kim
Il-Shin
IS
Kim
Jae Ho
JH
Han
Mi Young
MY
Ryu
Sung Ho
SH
Patterson
Randen L
RL
Snyder
Solomon H
SH
Suh
Pann-Ghill
PG
D000818:Animals; D001921:Brain / Q000378:metabolism; D049109:Cell Proliferation; D002966:Clathrin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D034284:Dynamin I / Q000378:metabolism*; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D017930:Genes, Reporter; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D047468:Immunoprecipitation; D016716:PC12 Cells; D051966:Phospholipase C gamma; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D010738:Type C Phospholipases / Q000502:physiology*; D015854:Up-Regulation; D018909:src Homology Domains
D002966:Clathrin; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D006160:Guanosine Triphosphate; D066246:ErbB Receptors; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D034284:Dynamin I