Stathmin interaction with HSC70 family proteins.
Stathmin is a ubiquitous cytosolic phosphoprotein participating in the relay and integration of diverse intracellular signaling pathways involved in the control of cell proliferation, differentiation, and activities. It is phosphorylated in response to diverse extracellular signals including hormones and growth factors, and it is highly expressed during development and in diverse tumoral cells and tissues. Stathmin interacts with tubulin and other potential protein partners such as BiP, KIS, CC1 and CC2/tsg101. In our present search for further functional partners of stathmin, we identified proteins in the Hsp70 family, and in particular Hsc70, as interacting with stathmin in vitro. Hsc70 is among the proteins coimmunoprecipitated with stathmin, and it is the main protein retained specifically on stathmin-Sepharose beads identified by one- and two-dimensional electrophoresis and immunoblots. Bovine serum albumin (BSA)-Sepharose did not bind Hsc70, and anti-stathmin antisera specifically inhibited the interaction of Hsc70 with stathmin-Sepharose. The binding of Hsc70 to stathmin is dependent on the phosphorylation status of stathmin, as it did not occur with a "pseudophosphorylated" mutant form of stathmin. This interaction is further dependent on the ATP status of Hsc70. It was inhibited in the presence of ATP-Mg++ but not in the presence of ATP-Mg++ and ethylenediaminetetraacetic acid (EDTA) or of ADP. Our results suggest that the interaction of stathmin with Hsc70 is specific in both proteins and most likely biologically relevant in the context of their functional implication in the control of numerous intracellular signaling and regulatory pathways, and hence of normal cell growth and differentiation.
Manceau
V
V
INSERM U440-IFM, Paris, France.
Gavet
O
O
Curmi
P
P
Sobel
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D008868:Microtubule Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D050777:Stathmin
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D008868:Microtubule Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin; D000255:Adenosine Triphosphate