A tyrosine phosphatase is associated with the somatostatin receptor.
Regulation of tyrosine phosphorylation is thought to be an essential step in signal transduction mechanisms that mediate cellular responses. In pancreatic tumour cells we demonstrated that somatostatin analogues inhibited cell proliferation and stimulated a membrane protein tyrosine phosphatase (PTP) activity at concentrations at which they bind to the somatostatin receptor. To elucidate the role of PTP in the signal transduction pathway activated by somatostatin receptors we first studied the interaction of PTP with the somatostatin receptor at the membrane. We purified somatostatin receptors by immunoaffinity from pancreatic membranes that strongly expressed the type 2 somatostatin receptor sstr2. We identified the receptor as an 87 kDa protein. We demonstrated that a PTP activity co-purified with somatostatin receptors. The PTP was identified as a 66 kDa protein immunoreactive to antibodies against SHPTP1. These antibodies immunoprecipitated somatostatin receptors either occupied or unoccupied by ligand indicating that SHPTP1 is associated with somatostatin receptors. We then expressed sstr2A in monkey kidney COS-7 cells and mouse NIH/3T3 fibroblasts and demonstrated that somatostatin analogues (RC 160, octreotide and BIM 23014) which exhibited high affinity for sstr2 stimulated a PTP activity and inhibited cell proliferation in proportion to their affinities for sstr2. Under the same conditions these analogues have no effect on the growth of cells expressing sstr1. All these results suggest that a PTP related to SHPTP1 is associated with somatostatin receptors and may be involved in the negative growth signal promoted by sstr2.
Delesque
N
N
INSERM U151, Institut Louis Bugnard, CHU Rangueil, Toulouse, France.
Buscail
L
L
Estève
J P
JP
Rauly
I
I
Zeggari
M
M
Saint-Laurent
N
N
Bell
G I
GI
Schally
A V
AV
Vaysse
N
N
Susini
C
C
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D000882:Haplorhini; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017481:Receptors, Somatostatin / Q000502:physiology*; D015398:Signal Transduction
D017481:Receptors, Somatostatin; D017027:Protein Tyrosine Phosphatases