Grb2 negatively regulates epidermal growth factor-induced phospholipase C-gamma1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-gamma1. 2005

Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
Department of Life Science, Pohang University of Science and Technology, San 31, Hyojadong, Pohang, Kyungbuk, 790-784, South Korea.

Phospholipase C-gamma1 (PLC-gamma1) plays pivotal roles in cellular growth and proliferation. Upon the stimulation of growth factors and hormones, PLC-gamma1 is rapidly phosphorylated at three known sites; Tyr771, Tyr783 and Tyr1254 and its enzymatic activity is up-regulated. In this study, we demonstrate for the first time that Grb2, an adaptor protein, specifically interacts with tyrosine-phosphorylated PLC-gamma1 at Tyr783. The association of Grb2 with PLC-gamma1 was induced by the treatment with epidermal growth factor (EGF). Replacement of Tyr783 with Phe completely blocked EGF-induced interaction of PLC-gamma1 with Grb2, indicating that tyrosine phosphorylation of PLC-gamma1 at Tyr783 is essential for the interaction with Grb2. Interestingly, the depletion of Grb2 from HEK-293 cells by RNA interference significantly enhanced increased EGF-induced PLC-gamma1 enzymatic activity and mobilization of the intracellular Ca2+, while it did not affect EGF-induced tyrosine phosphorylation of PLC-gamma1. Furthermore, overexpression of Grb2 inhibited PLC-gamma1 enzymatic activity. Taken together, these results suggest Grb2, in addition to its key function in signaling through Ras, may have a negatively regulatory role on EGF-induced PLC-gamma1 activation.

UI MeSH Term Description Entries
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010738 Type C Phospholipases A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS. Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D014443 Tyrosine A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin. L-Tyrosine,Tyrosine, L-isomer,para-Tyrosine,L Tyrosine,Tyrosine, L isomer,para Tyrosine

Related Publications

Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
April 2003, Molecules and cells,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
December 2003, The Biochemical journal,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
August 2010, Biochemical and biophysical research communications,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
January 1998, Molecular and cellular biology,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
March 2005, Proceedings of the National Academy of Sciences of the United States of America,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
March 1990, The Journal of biological chemistry,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
October 2006, The Journal of biological chemistry,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
June 2010, Biochemical and biophysical research communications,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
May 2003, The Journal of biological chemistry,
Jang Hyun Choi, and Won-Pyo Hong, and Sanguk Yun, and Hyeon Soo Kim, and Jong-Ryul Lee, and Jong Bae Park, and Yun Soo Bae, and Sung Ho Ryu, and Pann-Ghill Suh
May 2006, Molecular biology of the cell,
Copied contents to your clipboard!