Novel polypeptide of protein p140 and DNAs encoding it

Abstract

The present invention is related to a novel protein p140 polypeptide which is a key protein involved in the signal transmission system of insulin; method for preparation of it; DNA encoding the said polypeptide; vector derived the said DNA; host cells transformed the said vector; antibody of the said polypeptide; pharmaceutical composition containing the said peptide or antibody; method for the prevention and/or treatment of diabetes, which is characterized by tyrosine phosphorylation of the said protein p140; agent for the prevention and/or treatment for the currently said the prevention and/or treatment method; agent for the prevention and/or treatment of diabetes, which is characterized by containing a compound which can tyrosine phosphorylation of protein p140, as active ingredient and the screening methods of the said prevention and/or treatment agent. Tyrosine phosphorylation of protein p140 is an essential step in the induction of hypoglycemia by glucose uptake. Method and agent of prevention and/or treatment based on tyrosine phosphorylation of protein p140 in the present invention is not only improve the diabetes-derived hyperglycemic conditions but are also useful for the treatment and/or prevention of diabetes, especially non-insulin dependent diabetes mellitus (NIDDM).

1 . A polypeptide of protein p140 having the amino acid sequence shown in SEQ ID No. 1 in substantially purified form, a homologue thereof or a fragment of the sequence or homologue of a fragment.  
     
     
         2 . A polypeptide according to  claim 1  having the amino acid sequence shown in SEQ ID No. 1.  
     
     
         3 . DNA encoding a polypeptide according to  claim 1 .  
     
     
         4 . DNA according to  claim 3  having the, nucleotide sequence shown in SEQ ID No. 2 or a fragment thereof capable of selectively hybridizing to SEQ ID No. 2.  
     
     
         5 . DNA according to  claim 3  having the nucleotide sequence shown in SEQ ID No. 3 or a fragment thereof capable of selectively hybridizing to SEQ ID No. 3.  
     
     
         6 . A replication and expression vector comprising DNA according to any one of  claims 3  to  5 .  
     
     
         7 . Host cells transformed or transfected with a replication and expression vector according to  claim 6 .  
     
     
         8 . A method of producing a polypeptide which comprises culturing host cells according to  claim 7  under conditions effective to express a polypeptide according to  claim 1  or  2 .  
     
     
         9 . A monoclonal or polyclonal antibody to a polypeptide according to  claim 1  or  2 .  
     
     
         10 . A pharmaceutical composition containing a polypeptide according to claims  1  or  2  or an antibody according to  claim 9  in association with a pharmaceutically acceptable diluent and/or carrier.  
     
     
         11 . An agent for the prevention and/or treatment of diabetes containing a polypeptide according to claims  1  or  2 .  
     
     
         12 . A method for the prevention and/or treatment of diabetes, which is characterized of tyrosine phosphorylation of protein p140.  
     
     
         13 . An agent for the prevention and/or treatment of diabetes, which characterized of tyrosine phosphorylation of protein p140.  
     
     
         14 . An agent for the prevention and/or treatment of diabetes characterized by containing a compound which can tyrosine phosphorylation of protein p140, as active ingredient.  
     
     
         15 . A method for the screening of the agent for the prevention and/or treatment of diabetes, which is characterized by using protein p140.