Protein-tyrosine phosphatase 1B mediates the effects of insulin on the actin cytoskeleton in immortalized fibroblasts.
Insulin regulates diverse cellular responses including actin reorganization. The mechanism by which insulin induces formation of lamellipodia in cultured cells is not known but is likely to involve activation of Src family protein-tyrosine kinases. Here we show that protein-tyrosine phosphatase 1B (PTPIB) activates Src, thereby initiating the activation of a Rac-dependent pathway leading to cytoskeletal remodeling. Conversely, expression of a proline to alanine (P309,310A) PTP1B mutant, which cannot activate Src, fails to activate Rho GTPases or cause changes in actin organization. Rat fibroblasts lacking PTP1B expression do not activate Src or Rac in response to insulin and cannot reorganize actin. These results show that PTP1B, best known as a negative regulator of the metabolic effects of insulin, is required for the effects of insulin on actin organization in immortalized fibroblasts.
Dadke
Shrikrishna
S
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497, USA.
Chernoff
Jonathan
J
D000199:Actins / Q000378:metabolism*; D000409:Alanine / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D018909:src Homology Domains
D000199:Actins; D007328:Insulin; D011993:Recombinant Fusion Proteins; D011392:Proline; D005982:Glutathione Transferase; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat; D020558:GTP Phosphohydrolases; D020741:rho GTP-Binding Proteins; D000409:Alanine