1. Ph.D. with 6 years of postdoctoral experience
2. Expeience in Signal Transduction/Immunology
3. Attached my CV
4. Please E-Mail your reply to Raghuk at ix.netcom.com
Thanks.
Panchamoorthy, Ph.D.
Curriculum Vitae
Name: Govindaswamy Panchamoorthy
Address: 1575 Tremont Street, Apt # 901, Boston, MA 02120
Phone: 617-566-0355 (home); 617-432-4979 (work)
Visa Status: Permanent Resident
Education:
1989 Ph.D. Biochemistry - All India Institute of Medical Sciences, New Delhi, India.
1982 M.Sc. Life Sciences - Jawaharlal Nehru University, New Delhi, India.
1980 B.Sc. Chemistry - University of Madras, India.
Postdoctoral Training:
Research Fellowships:
1992-present Research Fellow, Lymphocyte Biology Section, Brigham and
Women's Hospital, Harvard Medical School, Boston, MA
1990-1992 Research Fellow, Laboratory of Immunochemistry, Dana-Farber
Cancer Institute, Harvard Medical School, Boston, MA
1988-1989 Research Associateship from Department of Science and
Technology, Government of India, New Delhi
Awards and Honors:
1993-1995 Research fellowship award from The Medical Foundation/Charles A. King Trust, Boston, MA.
1982-1988 Junior Research Fellowship from Indian Council of Medical Research.
1980-1982 Merit Scholarship from Jawaharlal Nehru University, New Delhi, India.
1976-1980 Government of India National Merit Loan Scholarship
Memberships:
1993-present American Association for the Advancement of Science
1983-1989 Indian Immunology Society
1982-1989 Society of Young Scientists, New Delhi.
Teaching Experience:
1983-1989 Taught theory and practicals in immunology and biochemistry for
medical (M.B.B.S) and undergraduate (Human Biology) students,
All India Institute of Medical Sciences, New Delhi, India
Publications:
Original Articles:
1. Panchamoorthy G, Fukazawa T, Stolz L, Payne G, Reedquist K, Shoelson S, Songyang Z,
Cantley L, Walsh C and Band H. Physical and functional interactions between SH2 and
SH3 domains of the Src family protein tyrosine kinase p59fyn. Mol. Cell. Biol. 1994;
14: 6372.
2. Reedquist K, Fukazawa T, Druker B, Panchamoorthy G, Shoelson s, and Band H.
Rapid T-cell receptor-mediated tyrosine phosphorylation of p120, an Fyn/Lck
Src homology 3 domain-binding protein. Proc. Natl. Acad. Sci. USA. 1994; 91: 4135.
3. Fukazawa T, Reedquist K, Trub T, Soltof S, Panchamoorhty G, Druker B,
Cantley L, Shoelson S, Band H. SH3 domain binding T cells tyrosyl
phosphoprotein p120: identity with c-cbl protoncogene product and in vivo
complexes with Grb2 and PI3-kinase. (J. Biol. Chem. In press).
4. Panchamoorthy G, McLean J, Modlin RL, Morita CT, Ishikawa S, Brenner MB,
Band H. A Predominance of the T Cell Receptor Vþ2/Vë2 Subset in Human
Mycobacteria-Responsive T Cells Suggests Germline Gene Encoded Recognition.
J Immunol. 1991; 147:3360.
5. Uyemura K, Deans RJ, Band H, Ohmen J, Panchamoorthy G, Morita CT, Rea
TH, Modlin RL. Evidence for clonal selection of þë T-cells in response to a
human pathogen. J. Exp. Med. 1991; 174:683.
6. Band H, Porcelli SA, Panchamoorthy G, McLean J, Morita CT, Ishikawa S,
Modlin R, Brenner MB. Antigens and antigen-presenting molecules for þë T
cells. Current Topics in Microbiology and Immunology. 1991; 173:229.
7. Band H, Panchamoorthy G, McLean J, Morita CT, Ishikawa S, Modlin R, Brenner
MB. Recognition of mycobacterial antigens by þë T cells. 33rd Forum in
Immunology on "þë T Cells", Lefranc, M-P, Bonneville M, eds. Research in
Immunology. 1990; 141:645.
8. Panchamoorthy G, Tiwari SC, and Srivastava LM. Inherited structural and
quantitative polymorphisms of C3b receptor (CR1) in normals and patients with
glomerular diseases. Asian Pac J Allergy Immunol. 1993; 11:123.
9. Panchamoorthy G, Tewari SC, Bora NS, Srivastava LM. Decreased expression
of C3b receptor (CR1) on the erythrocytes of patients with acute
glomerulonephritis. Clin Chem Enzym Comms. 1990; 2:167.
10. Srivastava LM, Panchamoorthy G, Saibaba KSS. Relevance of complement
system in clinical biochemistry. Proc Assoc Clin Biochem of India. 1989; 34.
11. Das N, Bora NS, Panchamoorthy G, Srivastava LM. Circulating immune
complexes in myocardial infarction. Ind J Med Res. 1987; 86:74.
12. Fukazawa T, Panchamoorthy G, Shoelson S, and Band H. Phosphotyrosyl
Peptide-sensitive Binding of a Non-Phosphotyrosyl Protein, pp32 to SH2 Domain
of FynB Binding of a non-phosphotyrosyl polypeptide pp32 to Fyn SH2 domain.
In preparation.
13. Fukazawa T, Reedquist K, Panchamoorthy G, Soltoff S, Trub T, Druker B,
Cantley L, Shoelson S, Band H. T cell activation-dependent association between
p85 subunit of the PI 3-kinase and Grb2/PLC 1-binding phosphotyrosyl protein
pp36/38. (submitted to J. Biol. Chem.)
14. Reedquist K, Fukazawa T, Panchamoorthy G, Druker B, Band H. Stimulation
through the T cell receptor induces p120cbl association with crk proteins.
(Submitted to J. Biol. Chem.)
15. Panchamoorhty G, Fukazawa T, Soltoff S, Reedquist K, Cantley L, Band H.
p120cbl is a major tyrosine phosphorylation substrate upon triggering through
B cell antigen receptor and forms in vivo complexes with multiple signalling
proteins. In preparation.
16. Panchamoorthy G, Reedquist K, David V, Reeves W, Anderson C and Band H. Ku,
the regulatory subunit of DNA-dependent protein kinase, forms a multi-protein
complex. In preparation.
Papers Presented in Symposia/Conferences:
1. Panchamoorthy G, Srivastava N, Gupta SP, Srivastava LM. Evaluation of
complement (C3) inhibition in vitro by drugs used in management of bronchial
asthma. Proc 11th Ann Conf of Indian Immunol Soc. Hyderabad, India, 1985.
2. Panchamoorthy G, Bora NS, Srivastava LM. Genetic polymorphism of C3b
receptor (CR1) in Indian population. Proc 6th Internatl Cong of Immunol.
Toronto, Canada. 1986.
3. Das N, Bora NS, Panchamoorthy G, Kazmi S, Srivastava LM. Circulating
immune complex in myocardial infarction. Proc 6th Internatl Cong of Immunol.
Toronto, Canada. 1986.
4. Panchamoorthy G, Bora NS, Srivastava LM. Erythrocyte C3b receptor (CR1)
levels in normal Indian population. Proc 14th Ann Conf of Indian Immunol Soc.
Srinagar, India. 1987.
5. Srivastava LM, Tiwari SC, Panchamoorthy G, Bora NS. Acquired deficiency of
C3b receptor (CR1) in acute glomerulonephritis. Proc 7th Internatl Cong in
Immunol. Berlin, FRG, 1989.
6. Panchamoorthy G, Tiwari SC, Bora NS, Srivastava LM. Structural
polymorphisms of C3b receptor (CR1) in normal North Indian population and
patients with renal diseases. Proc 16th Ann Conf of Indian Immunol Soc. 1989.
7. Morita CT, Band H, Panchamoorthy G, Brenner MB. A major subset of human
þë T cells reactive to mycobacterium tuberculosis is not restricted by classical
MHC molecules. J Cellular Biochem Supplement 16D: 68. Presented at the
Keystone Symposium on Antigen Presentation Functions of the MHC, March 1992.
8. Wagner LE, Romzek NC, Panchamoorthy G, Band H, Holoshitz J. A heat shock
protein-derived peptide enhances anti-tumor cytolytic activity of human þë T
cell clones. Presented at the Annual Symposium of American Federation of
Clinical Research, November 1992.
Research Experience
Lymphocyte signal transduction
Antigen recognition by þë T cell receptor
Complement system and complement receptor
Biochemical characterization of autoantigen, Ku and associated proteins
Expertise
Cellular and Molecular Immunology and Immunochemistry
Cell Biology and Biochemistry
Molecular Biology/Genetic Engineering
References
Hamid Band, M.D., Ph.D.
Assistant Professor of Medicine
Lymphocyte Biology Section
Department of Rheumatology and Immunology
Brigham and Women's Hospital
Boston, MA 02115
Telephone: 617-432-1557
Michael B. Brenner, M.D.
Chief, Lymphocyte Biology Section
Department of Rheumatology and Immunology
Brigham and Women's Hospital
Boston, MA 02115
Telephone: 617-432-0614
Harout Dersimonian, Ph.D.
Assistant Professor
Transplantation Biology Research Center
Massachusetts General Hospital
MGH East, Bldg 149, Rm 9019
Charlestown, MA 02129
Telephone: 617-726-4362
Anjana Rao, Ph.D.
Associate Professor of pathology
Division of Tumor Virology
Dana-Farber Cancer Institute
44 Binney Street
Boston, MA 02115.
Telephone: 617-375-8265
Christina M. Parker, M.D.
Assistant Professor of Medicine
Department of Rheumatology and Immunology
Brigham and Women's Hospital
Boston, MA 02115
Telephone: 617-432-4971
Current Research Projects:
Biochemical and functional characterization of a novel Fyn SH3 domain-binding
protein
My current research project is focussed on the understanding of molecular
events involved in T cell receptor mediated signalling which involves protein
tyrosine kinases. One of the earliest identifiable biochemical events in response to
stimulation through T cell receptor (TCR) is the tyrosine phosphorylation of cellular
proteins including the receptor components. Two src-family tyrosine kinases p59fyn
(Fyn) and p56lck (Lck) have been shown to play important roles in T cell signalling.
Similar to other src-family tyrosine kinases, Fyn and Lck possess an N-terminal
myristylation signal that is essential for membrane anchoring, followed by a unique
domain that mediates binding to CD3 and þ chains or CD4/8. This region is followed
by non-catalytic Src-homology (SH3 and 2) domains, a highly conserved tyrosine
kinase domain, and a C-terminal domain that carries a negative regulatory tyrosine
phosphorylation site. The SH2 domains bind tyrosine phosphorylated motifs and thus
participate in the formation of activated signalling complexes. The SH3 domains bind
proline-rich motifs and mediate phosphorylation independent protein-protein
interactions. I have shown that the SH2 and SH3 domains of the tyrosine kinase
physically interact with each other and play a regulatory role on T cell signalling
(Mol. Cell. Biol, 1994; 14:6372). Specific ligand binding to one domain influences the
other domain in terms of its binding to cellular target proteins which control the
effector functions of the cell in response to antigens. Thus, the interaction of SH2
and SH3 domains suggest a novel mechanism of regulating the enzymatic activity of
src kinases and their interaction with other proteins.
Deletion of SH3 domain among src-family kinases reveals their transforming
potential, suggesting SH3 domain has a negative regulatory role. Thus,
identification and characterization cellular proteins that interact with SH3 domains
of src-family tyrosine kinases is likely to lead to significant insights into the role of
these proteins in T cell signal transduction and may reveal the mechanisms of their
oncogenic transformation.
I have developed a novel method for screening þExlox expression library to clone
specific genes encoding proteins that bind to Fyn SH3 domain and may therefore be
involved in T cell signalling in response to foreign antigen. I have used bacterially
expressed Fyn SH3 domain as a fusion protein with GST as a probe to screen the
library. One cDNA clone was found repeatedly and the open reading frame cDNA
fragments have proline-rich motifs which are characteristic of SH3 domain binding
proteins. Search for sequence identity or homologous sequences from the database
did not provide any matching sequences suggesting that the cDNA fragments
obtained from the library repesent a novel SH3 domain-binding protein. I have raised
antibodies against these proteins by injecting rabbits with GST fusion proteins
obtained from these partial cDNA clones. Currently, I am trying to isolate the full
length cDNA clones for these proteins and simultaneously characterize these SH3
binding proteins using the antibodies.
Characterization of c-cbl protooncogene in lymphocyte signal transduction
We have previously identified p120 as a Fyn/Lck SH3 domain binding protein
which is tyrosine phosphorylated very early following TCR triggering (Proc. Natl.
Acad. Sci. USA. 1994; 91: 4135). Further, using direct protein purification, amino
acid sequence analysis, reactivity with antibodies and 2D-gel analysis we have
identified p120 as the human c-cbl protooncogene product (communicated to Mol.
Cell. Biol.). p120cbl possesses a large proline-rich region with multiple putative
SH3-binding motifs and this region is included in the deletion that renders v-cbl
oncogenic. p120cbl forms in vivo complexes with three SH2/SH3 domain-bearing
signalling proteins: Fyn, Grb2, and p85 subunit of PI3-kinase. Currently we are
trying to delineate the receptor-mediated lymphocyte signalling pathways involving
p120cbl and characterizing the role of p120cbl in oncogenesis. Curriculum
Vitae
Name: Govindaswamy Panchamoorthy
Address: 1575 Tremont Street, Apt # 901, Boston, MA 02120
Phone: 617-566-0355 (home); 617-432-4979 (work)
Visa Status: Permanent Resident
Education:
1989 Ph.D. Biochemistry - All India Institute of Medical Sciences, New Delhi,
India.
1982 M.Sc. Life Sciences - Jawaharlal Nehru University, New Delhi, India.
1980 B.Sc. Chemistry - University of Madras, India.
Postdoctoral Training:
Research Fellowships:
1992-present Research Fellow, Lymphocyte Biology Section, Brigham and
Women's Hospital, Harvard Medical School, Boston, MA
1990-1992 Research Fellow, Laboratory of Immunochemistry, Dana-Farber
Cancer Institute, Harvard Medical School, Boston, MA
1988-1989 Research Associateship from Department of Science and
Technology, Government of India, New Delhi
Awards and Honors:
1993-1995 Research fellowship award from The Medical Foundation/Charles A. King Trust, Boston, MA.
1982-1988 Junior Research Fellowship from Indian Council of Medical Research.
1980-1982 Merit Scholarship from Jawaharlal Nehru University, New Delhi, India.
1976-1980 Government of India National Merit Loan Scholarship
Memberships:
1993-present American Association for the Advancement of Science
1983-1989 Indian Immunology Society
1982-1989 Society of Young Scientists, New Delhi.
Teaching Experience:
1983-1989 Taught theory and practicals in immunology and biochemistry for
medical (M.B.B.S) and undergraduate (Human Biology) students,
All India Institute of Medical Sciences, New Delhi, India
Publications:
Original Articles:
1. Panchamoorthy G, Fukazawa T, Stolz L, Payne G, Reedquist K, Shoelson S, Songyang Z,
Cantley L, Walsh C and Band H. Physical and functional interactions between SH2 and
SH3 domains of the Src family protein tyrosine kinase p59fyn. Mol. Cell. Biol. 1994;
14: 6372.
2. Reedquist K, Fukazawa T, Druker B, Panchamoorthy G, Shoelson s, and Band H.
Rapid T-cell receptor-mediated tyrosine phosphorylation of p120, an Fyn/Lck
Src homology 3 domain-binding protein. Proc. Natl. Acad. Sci. USA. 1994; 91: 4135.
3. Fukazawa T, Reedquist K, Trub T, Soltof S, Panchamoorhty G, Druker B,
Cantley L, Shoelson S, Band H. SH3 domain binding T cells tyrosyl
phosphoprotein p120: identity with c-cbl protoncogene product and in vivo
complexes with Grb2 and PI3-kinase. (J. Biol. Chem. In press).
4. Panchamoorthy G, McLean J, Modlin RL, Morita CT, Ishikawa S, Brenner MB,
Band H. A Predominance of the T Cell Receptor Vþ2/Vë2 Subset in Human
Mycobacteria-Responsive T Cells Suggests Germline Gene Encoded Recognition.
J Immunol. 1991; 147:3360.
5. Uyemura K, Deans RJ, Band H, Ohmen J, Panchamoorthy G, Morita CT, Rea
TH, Modlin RL. Evidence for clonal selection of þë T-cells in response to a
human pathogen. J. Exp. Med. 1991; 174:683.
6. Band H, Porcelli SA, Panchamoorthy G, McLean J, Morita CT, Ishikawa S,
Modlin R, Brenner MB. Antigens and antigen-presenting molecules for þë T
cells. Current Topics in Microbiology and Immunology. 1991; 173:229.
7. Band H, Panchamoorthy G, McLean J, Morita CT, Ishikawa S, Modlin R, Brenner
MB. Recognition of mycobacterial antigens by þë T cells. 33rd Forum in
Immunology on "þë T Cells", Lefranc, M-P, Bonneville M, eds. Research in
Immunology. 1990; 141:645.
8. Panchamoorthy G, Tiwari SC, and Srivastava LM. Inherited structural and
quantitative polymorphisms of C3b receptor (CR1) in normals and patients with
glomerular diseases. Asian Pac J Allergy Immunol. 1993; 11:123.
9. Panchamoorthy G, Tewari SC, Bora NS, Srivastava LM. Decreased expression
of C3b receptor (CR1) on the erythrocytes of patients with acute
glomerulonephritis. Clin Chem Enzym Comms. 1990; 2:167.
10. Srivastava LM, Panchamoorthy G, Saibaba KSS. Relevance of complement
system in clinical biochemistry. Proc Assoc Clin Biochem of India. 1989; 34.
11. Das N, Bora NS, Panchamoorthy G, Srivastava LM. Circulating immune
complexes in myocardial infarction. Ind J Med Res. 1987; 86:74.
12. Fukazawa T, Panchamoorthy G, Shoelson S, and Band H. Phosphotyrosyl
Peptide-sensitive Binding of a Non-Phosphotyrosyl Protein, pp32 to SH2 Domain
of FynB Binding of a non-phosphotyrosyl polypeptide pp32 to Fyn SH2 domain.
In preparation.
13. Fukazawa T, Reedquist K, Panchamoorthy G, Soltoff S, Trub T, Druker B,
Cantley L, Shoelson S, Band H. T cell activation-dependent association between
p85 subunit of the PI 3-kinase and Grb2/PLC 1-binding phosphotyrosyl protein
pp36/38. (submitted to J. Biol. Chem.)
14. Reedquist K, Fukazawa T, Panchamoorthy G, Druker B, Band H. Stimulation
through the T cell receptor induces p120cbl association with crk proteins.
(Submitted to J. Biol. Chem.)
15. Panchamoorhty G, Fukazawa T, Soltoff S, Reedquist K, Cantley L, Band H.
p120cbl is a major tyrosine phosphorylation substrate upon triggering through
B cell antigen receptor and forms in vivo complexes with multiple signalling
proteins. In preparation.
16. Panchamoorthy G, Reedquist K, David V, Reeves W, Anderson C and Band H. Ku,
the regulatory subunit of DNA-dependent protein kinase, forms a multi-protein
complex. In preparation.
Papers Presented in Symposia/Conferences:
1. Panchamoorthy G, Srivastava N, Gupta SP, Srivastava LM. Evaluation of
complement (C3) inhibition in vitro by drugs used in management of bronchial
asthma. Proc 11th Ann Conf of Indian Immunol Soc. Hyderabad, India, 1985.
2. Panchamoorthy G, Bora NS, Srivastava LM. Genetic polymorphism of C3b
receptor (CR1) in Indian population. Proc 6th Internatl Cong of Immunol.
Toronto, Canada. 1986.
3. Das N, Bora NS, Panchamoorthy G, Kazmi S, Srivastava LM. Circulating
immune complex in myocardial infarction. Proc 6th Internatl Cong of Immunol.
Toronto, Canada. 1986.
4. Panchamoorthy G, Bora NS, Srivastava LM. Erythrocyte C3b receptor (CR1)
levels in normal Indian population. Proc 14th Ann Conf of Indian Immunol Soc.
Srinagar, India. 1987.
5. Srivastava LM, Tiwari SC, Panchamoorthy G, Bora NS. Acquired deficiency of
C3b receptor (CR1) in acute glomerulonephritis. Proc 7th Internatl Cong in
Immunol. Berlin, FRG, 1989.
6. Panchamoorthy G, Tiwari SC, Bora NS, Srivastava LM. Structural
polymorphisms of C3b receptor (CR1) in normal North Indian population and
patients with renal diseases. Proc 16th Ann Conf of Indian Immunol Soc. 1989.
7. Morita CT, Band H, Panchamoorthy G, Brenner MB. A major subset of human
þë T cells reactive to mycobacterium tuberculosis is not restricted by classical
MHC molecules. J Cellular Biochem Supplement 16D: 68. Presented at the
Keystone Symposium on Antigen Presentation Functions of the MHC, March 1992.
8. Wagner LE, Romzek NC, Panchamoorthy G, Band H, Holoshitz J. A heat shock
protein-derived peptide enhances anti-tumor cytolytic activity of human þë T
cell clones. Presented at the Annual Symposium of American Federation of
Clinical Research, November 1992.
Research Experience
Lymphocyte signal transduction
Antigen recognition by þë T cell receptor
Complement system and complement receptor
Biochemical characterization of autoantigen, Ku and associated proteins
Expertise
Cellular and Molecular Immunology and Immunochemistry
Cell Biology and Biochemistry
Molecular Biology/Genetic Engineering
References
Hamid Band, M.D., Ph.D.
Assistant Professor of Medicine
Lymphocyte Biology Section
Department of Rheumatology and Immunology
Brigham and Women's Hospital
Boston, MA 02115
Telephone: 617-432-1557
Michael B. Brenner, M.D.
Chief, Lymphocyte Biology Section
Department of Rheumatology and Immunology
Brigham and Women's Hospital
Boston, MA 02115
Telephone: 617-432-0614
Harout Dersimonian, Ph.D.
Assistant Professor
Transplantation Biology Research Center
Massachusetts General Hospital
MGH East, Bldg 149, Rm 9019
Charlestown, MA 02129
Telephone: 617-726-4362
Anjana Rao, Ph.D.
Associate Professor of pathology
Division of Tumor Virology
Dana-Farber Cancer Institute
44 Binney Street
Boston, MA 02115.
Telephone: 617-375-8265
Christina M. Parker, M.D.
Assistant Professor of Medicine
Department of Rheumatology and Immunology
Brigham and Women's Hospital
Boston, MA 02115
Telephone: 617-432-4971
Current Research Projects:
Biochemical and functional characterization of a novel Fyn SH3 domain-binding
protein
My current research project is focussed on the understanding of molecular
events involved in T cell receptor mediated signalling which involves protein
tyrosine kinases. One of the earliest identifiable biochemical events in response to
stimulation through T cell receptor (TCR) is the tyrosine phosphorylation of cellular
proteins including the receptor components. Two src-family tyrosine kinases p59fyn
(Fyn) and p56lck (Lck) have been shown to play important roles in T cell signalling.
Similar to other src-family tyrosine kinases, Fyn and Lck possess an N-terminal
myristylation signal that is essential for membrane anchoring, followed by a unique
domain that mediates binding to CD3 and þ chains or CD4/8. This region is followed
by non-catalytic Src-homology (SH3 and 2) domains, a highly conserved tyrosine
kinase domain, and a C-terminal domain that carries a negative regulatory tyrosine
phosphorylation site. The SH2 domains bind tyrosine phosphorylated motifs and thus
participate in the formation of activated signalling complexes. The SH3 domains bind
proline-rich motifs and mediate phosphorylation independent protein-protein
interactions. I have shown that the SH2 and SH3 domains of the tyrosine kinase
physically interact with each other and play a regulatory role on T cell signalling
(Mol. Cell. Biol, 1994; 14:6372). Specific ligand binding to one domain influences the
other domain in terms of its binding to cellular target proteins which control the
effector functions of the cell in response to antigens. Thus, the interaction of SH2
and SH3 domains suggest a novel mechanism of regulating the enzymatic activity of
src kinases and their interaction with other proteins.
Deletion of SH3 domain among src-family kinases reveals their transforming
potential, suggesting SH3 domain has a negative regulatory role. Thus,
identification and characterization cellular proteins that interact with SH3 domains
of src-family tyrosine kinases is likely to lead to significant insights into the role of
these proteins in T cell signal transduction and may reveal the mechanisms of their
oncogenic transformation.
I have developed a novel method for screening þExlox expression library to clone
specific genes encoding proteins that bind to Fyn SH3 domain and may therefore be
involved in T cell signalling in response to foreign antigen. I have used bacterially
expressed Fyn SH3 domain as a fusion protein with GST as a probe to screen the
library. One cDNA clone was found repeatedly and the open reading frame cDNA
fragments have proline-rich motifs which are characteristic of SH3 domain binding
proteins. Search for sequence identity or homologous sequences from the database
did not provide any matching sequences suggesting that the cDNA fragments
obtained from the library repesent a novel SH3 domain-binding protein. I have raised
antibodies against these proteins by injecting rabbits with GST fusion proteins
obtained from these partial cDNA clones. Currently, I am trying to
isolate the full
length cDNA clones for these proteins and simultaneously characterize
these SH3
binding proteins using the antibodies.
Characterization of c-cbl protooncogene in lymphocyte signal
transduction
We have previously identified p120 as a Fyn/Lck SH3 domain binding
protein
which is tyrosine phosphorylated very early following TCR triggering
(Proc. Natl.
Acad. Sci. USA. 1994; 91: 4135). Further, using direct protein
purification, amino
acid sequence analysis, reactivity with antibodies and 2D-gel analysis
we have
identified p120 as the human c-cbl protooncogene product (communicated
to Mol.
Cell. Biol.). p120cbl possesses a large proline-rich region with
multiple putative
SH3-binding motifs and this region is included in the deletion that
renders v-cbl
oncogenic. p120cbl forms in vivo complexes with three SH2/SH3
domain-bearing
signalling proteins: Fyn, Grb2, and p85 subunit of PI3-kinase.
Currently we are
trying to delineate the receptor-mediated lymphocyte signalling
pathways involving
p120cbl and characterizing the role of p120cbl in oncogenesis.
