Annexin 2 has a dual role as regulator and effector of v-Src in cell transformation.
Cell transformation by v-Src involves rearrangement of the actin cytoskeleton, disassembly of focal adhesions, and the development of anchorage-independent growth. Here, we report that this is dependent on annexin 2, a v-Src substrate and calcium-dependent regulator of actin dynamics. Using a thermoactivatable mutant of v-Src, we show that at the permissive temperature, annexin 2 becomes phosphorylated and colocalizes with activated v-Src and focal adhesion kinase both at the plasma membrane and in a Rab11-positive compartment of the endosomal pathway. In cells depleted of annexin 2 by small interfering RNA, v-Src becomes activated at the permissive temperature but does not target to the plasma membrane or to perinuclear vesicles, and cell transformation does not occur. Our findings reveal a dual role for annexin 2, first as a regulator of v-Src trafficking and targeting and second as a v-Src effector in the reorganization of actin.
Hayes
Matthew J
MJ
Division of Cell Biology, University College London Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, United Kingdom.
Moss
Stephen E
SE
D000199:Actins / Q000378:metabolism; D000818:Animals; D017306:Annexin A2 / Q000378:metabolism / Q000502:physiology*; D017302:Annexins / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D000199:Actins; D017306:Annexin A2; D017302:Annexins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D034741:RNA, Small Interfering; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins