Human ALK protein tyrosine kinase

• US 5,770,421 A
• Filed: 10/12/1995
• Issued: 06/23/1998
• Est. Priority Date: 12/03/1993
• Status: Expired due to Term

• Current Assignee: St Jude Children's Research Hospital Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: St Jude Children's Research Hospital Incorporated (Abbott Laboratories Incorporated)
• Inventors: Look, A. Thomas, Morris, Stephan W.
• Primary Examiner(s): Hendricks, Keith D.
• Application Number:
  US08/542,363
• Time in Patent Office: 985 Days
• Field of Search: 435/194, 530/350, 530/324, 530/358, 530/352
• US Class Current: 435/194
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 9/12 transferring phosphorus containing groups, e.g. kinases (2.7)
• CPC Class Codes: Y10S 435/81 Packaged device or kit

Abstract

The present invention is based on the identification and sequence determination of a novel gene, ALK, which is fused to the gene encoding nucleophosmin (NPM) in translocations present in t(2;5) lymphoma cells. Based on homologies to other proteins, the amino acid sequence of the polypeptide encoded by the ALK (Anaplastic Lymphoma Kinase) gene is a membrane-spanning protein tyrosine kinase (PTK)/receptor. Antibodies to the ALK PTK/receptor and methods utilizing such antibodies are described, as are methods of using the ALK gene to isolate ligands for the ALK PTK/receptor.

Claims

1. An isolated human anaplastic lymphoma kinase (ALK) polypeptide, wherein said isolated ALK polypeptide

(a) has tyrosine kinase activity;

and

(b) renders an interleukin-3-dependent lymphoid cell line factor independent.

2. An isolated ALK polypeptide of claim 1, comprising a polypeptide having the amino acid sequence of SEQ ID NO:

2.

3. An isolated ALK polypeptide of claim 1, comprising a polypeptide having the amino acid sequence of SEQ ID NO:

4.

4. An isolated ALK polypeptide, comprising at least one structural domain of an ALK protein having the amino acid sequence of SEQ ID NO:

2, wherein said structural domain is selected from the group consisting of an extracellular domain, a transmembrane domain, a catalytic domain, a signal peptide domain, an intracellular domain, a kinase domain, an immunoreactive domain and a fusion domain.

5. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 27-1030 of SEQ ID NO:

2 as said extracellular domain.

6. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 1031-1058 of SEQ ID NO:

2 as said transmembrane domain.

7. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 1023-1376 of SEQ ID NO:

2 as said catalytic domain.

8. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 1-26 of SEQ ID NO:

2 as said signal peptide domain.

9. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 1059-1620 of SEQ ID NO:

2 as said intracellular domain.

10. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 605-1509 of SEQ ID NO:

2 as said kinase domain.

11. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 1359-1460 of SEQ ID NO:

2 as said immunoreactive domain.

12. An isolated ALK polypeptide according to claim 4, wherein said structural domain comprises amino acids 979-1078 of SEQ ID NO:

2 (corresponding to amino acids 1-100 of SEQ ID NO;

7) as said fusion domain.