The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit.
We have cloned a protein tyrosine kinase, MATK, which is expressed abundantly in megakaryocytes and the brain. We investigated whether MATK participates in the c-Kit ligand/stem cell factor (KL/SCF) signaling pathway in the megakaryocytic cell line CMK. After KL/SCF stimulation, five major proteins of molecular masses of 145, 113, 92, ... 76, and 63 kDa were rapidly and transiently tyrosine-phosphorylated in a time-dependent manner, peaking within 5 min, and returning to basal levels within 60 min. To study the role of MATK in the KL/SCF signaling pathway, glutathione S-transferase (GST) fusion proteins containing SH2 and SH3 domains of MATK were cloned, expressed in Escherichia coli, and purified. MATK-SH2, but not MATK-SH3, precipitated the tyrosine-phosphorylated c-Kit (molecular mass of 145 kDa) in KL/SCF-stimulated CMK cells. Other GST fusion proteins containing the SH2 domain of p85 of phosphatidylinositol 3-kinase, phospholipase C gamma-1, and ras-GAP also precipitated c-Kit. The tyrosine-phosphorylated c-Kit was co-immunoprecipitated with anti-MATK and anti-p85 antibodies in KL/SCF-stimulated CMK cells, but not in granulocyte-macrophage colony stimulating factor or interleukin-6-stimulated cells, suggesting receptor specificity. These results indicate that MATK associates with the c-Kit receptor following specific stimulation by KL/SCF via its SH2 domain and likely participates in transduction of growth signals induced by this cytokine in megakaryocytes.
Mesh Terms:
GTPase-Activating Proteins, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Cell Growth Factors, Humans, Interleukin-6, Megakaryocytes, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins pp60(c-src), Receptor Protein-Tyrosine Kinases, Receptors, Colony-Stimulating Factor, Stem Cell Factor, ras GTPase-Activating Proteins
GTPase-Activating Proteins, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Cell Growth Factors, Humans, Interleukin-6, Megakaryocytes, Protein-Tyrosine Kinases, Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins pp60(c-src), Receptor Protein-Tyrosine Kinases, Receptors, Colony-Stimulating Factor, Stem Cell Factor, ras GTPase-Activating Proteins
J. Biol. Chem.
Date: Apr. 21, 1995
PubMed ID: 7536744
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