The G protein G alpha(13) is required for growth factor-induced cell migration.
Heterotrimeric G proteins are critical cellular signal transducers. They are known to directly relay signals from seven-transmembrane G protein-coupled receptors (GPCRs) to downstream effectors. On the other hand, receptor tyrosine kinases (RTKs), a different family of membrane receptors, signal through docking sites in their carboxy-terminal tails created by autophosphorylated tyrosine residues. Here we show that a heterotrimeric G protein, G alpha(13), is essential for RTK-induced migration of mouse fibroblast and endothelial cells. G alpha(13) activity in cell migration is retained in a C-terminal mutant that is defective in GPCR coupling, suggesting that the migration function is independent of GPCR signaling. Thus, G alpha(13) appears to be a critical signal transducer for RTKs as well as GPCRs. This broader role of G alpha(13) in cell migration initiated by two types of receptors could provide a molecular basis for the vascular system defects exhibited by G alpha(13) knockout mice.
Shan
Dandan
D
Department of Physiology, Weill Medical College, Cornell University, New York, New York 10021, USA.
Chen
Lin
L
Wang
Dawei
D
Tan
Ying-Cai
YC
Gu
Jennifer L
JL
Huang
Xin-Yun
XY
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D005982:Glutathione Transferase; D020794:Receptor Protein-Tyrosine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020744:rac GTP-Binding Proteins