Abstract
The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR-ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions of this region were constructed to assess biologic effects of eliminating the CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show eradication of the direct interaction of CRKL with BCR-ABL in the proline deletion mutants. However, these BCR-ABL mutants transform myeloid cells to growth factor independence, and in these cells CRKL is tyrosine phosphorylated and associates with BCR-ABL. These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 119-126 |
| Number of pages | 8 |
| Journal | Leukemia and Lymphoma |
| Volume | 33 |
| Issue number | 1-2 |
| State | Published - 1999 |
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Keywords
- BCR-ABL
- CRKL
- Src homology domains
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research
Cite this
CRKL binding to BCR-ABL and BCR-ABL transformation. / Kolibaba, Kathryn S.; Bhat, Arun; Heaney, Conor; Oda, Tsukasa; Druker, Brian.
In: Leukemia and Lymphoma, Vol. 33, No. 1-2, 1999, p. 119-126.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CRKL binding to BCR-ABL and BCR-ABL transformation
AU - Kolibaba, Kathryn S.
AU - Bhat, Arun
AU - Heaney, Conor
AU - Oda, Tsukasa
AU - Druker, Brian
PY - 1999
Y1 - 1999
N2 - The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR-ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions of this region were constructed to assess biologic effects of eliminating the CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show eradication of the direct interaction of CRKL with BCR-ABL in the proline deletion mutants. However, these BCR-ABL mutants transform myeloid cells to growth factor independence, and in these cells CRKL is tyrosine phosphorylated and associates with BCR-ABL. These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.
AB - The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR-ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions of this region were constructed to assess biologic effects of eliminating the CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show eradication of the direct interaction of CRKL with BCR-ABL in the proline deletion mutants. However, these BCR-ABL mutants transform myeloid cells to growth factor independence, and in these cells CRKL is tyrosine phosphorylated and associates with BCR-ABL. These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.
KW - BCR-ABL
KW - CRKL
KW - Src homology domains
KW - Tyrosine phosphorylation
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UR - http://www.scopus.com/inward/citedby.url?scp=0033007404&partnerID=8YFLogxK
M3 - Article
C2 - 10194128
AN - SCOPUS:0033007404
VL - 33
SP - 119
EP - 126
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
SN - 1042-8194
IS - 1-2
ER -