Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Axl Receptor Tyrosine Kinase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1999

Noninsulin-dependent diabetes mellitus occurs in mice ectopically expressing the human Axl tyrosine kinase receptor.

The axl tyrosine kinase receptor is aberrantly expressed on myeloid cells of many individuals afflicted with chronic myelogenous leukemia (CML) and other myeloid leukemias. Although previous studies demonstrated this kinase to have oncogenic potential, it is not known whether axl actively participates in the onset and/or progression of CML. We addressed this question by generating transgenic mice possessing constitutive ectopic expression of human axl throughout cells of the myeloid hematopoietic lineage through the use of the granulocyte colony-stimulating factor (GCSF) receptor promoter. The transgenics did not exhibit hematopoietic malignancies, but did exhibit phenotypic characteristics associated with noninsulin-dependent diabetes mellitus (NIDDM) including hyperglycemia and hyperinsulinemia, severe insulin resistance, progressive obesity, hepatic lipidosis, and pancreatic islet dysplasia. The obese-diabetes phenotype was similar to that observed in the agouti and melanocortin-4(-/-) mutants, however the axl transgenics were not hyperphagic. Axl transgenic animals expressed elevated serum tumor necrosis factor (TNF)-alpha levels that were further enhanced upon in vitro lipopolysaccharide (LPS) stimulation of peripheral blood. Administration of the axl ligand, gas6, to peripheral transgenic blood samples eliminated excessive TNF-alpha production in response to LPS stimulation. As a means to better understand axl-gas6 biology, transgenic animals were produced which systemically expressed the gas6-binding axl proteolytic cleavage product. A more severe NIDDM phenotype occurred in these mice. The observed phenotypes may be related to the axl receptor or proteolytic cleavage product competing with related axl family receptors for binding of the gas6 ligand. We conclude that axl expression in myeloid cells in itself does not lead to the onset or progression of leukemia and suggest that ectopic axl expression affects endogenous modulation of TNF-alpha production indirectly resulting in the NIDDM phenotype.

Animals↗
PubMed1998

Determinants for transformation induced by the Axl receptor tyrosine kinase.

The Axl receptor tyrosine kinase is a transforming oncogene in NIH3T3 cells. In order to define structural requirements of the Axl receptor necessary for transformation we passaged recombinant retroviruses carrying the axl cDNA in NIH3T3 cells, generating randomly mutated axl variants. Using this strategy, we have isolated three axl viral strains (1B1, SV8, and FFa4) that show augmented 3T3 cell transforming capacity associated with elevated p140Axl. Upon sequencing, the 1B1 and SV8 proviruses possessed only silent mutations, making p140Axl overexpression the most likely explanation for their increased transformation activity. However, the characterization of FFa4 revealed a deletion of sequences encoding the carboxy-terminal 45 amino acids leading to the generation of a chimeric transcript comprised of a truncated Axl receptor with a segment of the 3' UTR region. Mutational analysis revealed that the transforming activity of FFa4 was specific to the formation of the chimeric receptor rather than to the carboxyl-terminal truncation. Intriguingly, none of the viral strains were able to transform the murine cell lines NR-6 and 32D despite equivalent expression of surface p140Axl protein. Further analysis showed that Axl's transforming potential is dependent on the host cell type, the presence of a putative pp190 as a facilitator for transformation, and the level of p140Axl expression. Taken together, these results underscore the complexity of Axl biology which is dependent on receptor stoichiometry and the cellular background.

3T3 Cells↗
PubMed2006

Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily.

Gas6 and protein S are two homologous secreted proteins that depend on vitamin K for their execution of a range of biological functions. A discrete subset of these functions is mediated through their binding to and activation of the receptor tyrosine kinases Axl, Sky and Mer. Furthermore, a hallmark of the Gas6-Axl system is the unique ability of Gas6 and protein S to tether their non receptor-binding regions to the negatively charged membranes of apoptotic cells. Numerous studies have shown the Gas6-Axl system to regulate cell survival, proliferation, migration, adhesion and phagocytosis. Consequently, altered activity/expression of its components has been detected in a variety of pathologies such as cancer and vascular, autoimmune and kidney disorders. Moreover, Axl overactivation can equally occur without ligand binding, which has implications for tumorigenesis. Further knowledge of this exquisite ligand-receptor system and the circumstances of its activation should provide the basis for development of novel therapies for the above diseases.

Animals↗
PubMed1997

GAS6 mediates adhesion of cells expressing the receptor tyrosine kinase Axl.

Axl is a receptor tyrosine kinase that contains both immunoglobulin and fibronectin III repeats in its extracellular domain reminiscent of cell adhesion molecules. Expression of the receptor tyrosine kinase Axl in the 32D myeloid cell line permits aggregation of cells in response to treatment with the native ligand GAS6; this aggregation was not observed in untreated 32D-Axl cells nor in treated parental cells. This aggregation can be blocked by the addition of excess Axl extracellular domain peptide and does not require intracellular Axl kinase activity. Cell surface binding activity of GAS6 was mapped to distinct plasma membrane interacting domains that are separate from the GAS6 motifs that engage the Axl receptor. This suggests that aggregation is mediated by a heterotypic intercellular mechanism whereby cell-bound GAS6 interacts with Axl receptor on an adjacent cell. This mechanism is supported by our observation that GAS6 binds to 32D parental cells which then permits their aggregation with untreated 32D-Axl cells. We have recently demonstrated that the GAS6-Axl interaction does not initiate mitogenesis in 32D cells. When considered with the adhesion results, these data suggest that an important biological function of the Axl-GAS6 interaction is to mediate cell-cell binding.

Animals↗
PubMed1997

Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor axl: potential role in autocrine signaling in cartilage.

OBJECTIVE: To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas-6, a protein product of growth-arrest-specific gene 6, and to determine if Gas-6 and axl function in the regulation of chondrocyte growth and survival. METHODS: The presence of Gas-6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes. The ability of recombinant Gas-6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined. Studies of the role of Gas-6 and axl in cell proliferation and survival were also performed. RESULTS: Both Gas-6 and axl were detected in cartilage by immunohistochemical staining. Gas-6 and axl messenger RNA (mRNA) and protein were also detected in cultures of primary and immortalized human chondrocytes. Compared with cells cultured in medium containing 10% serum, Gas-6 mRNA levels were increased in immortalized chondrocytes cultured in serum-free medium, while axl expression decreased. Chondrocytes attached to Gas-6-coated plastic, and the attachment was blocked by a soluble Ig fusion protein containing the axl extracellular domain. Recombinant human Gas-6 and serum-free conditioned medium from primary and immortalized human chondrocyte cultures stimulated chondrocyte axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized chondrocytes were stimulated with recombinant Gas-6 or when they were made to overexpress axl by transfection. Addition of recombinant Gas-6 to serum-free medium resulted in increased survival of primary chondrocytes cultured at low density in agarose. CONCLUSION: These findings present evidence for an autocrine signaling pathway in cartilage involving Gas-6 and the axl tyrosine kinase adhesion receptor. Stimulation of axl by Gas-6 may play an important role in the control of chondrocyte growth and survival.

3T3 Cells↗
PubMed1996

Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts.

Reversible growth arrest has been characterised for enhanced expression of a set of genes called gas (growth arrest specific). gas6 product (Gas6) is a secreted protein that was identified as the ligand for the tyrosine kinase receptor Axl. Here we report that Gas6 is able to induce cell cycle division entry in serum starved NIH3T3 cells. This mitogenic activity of Gas6 strictly correlates with its ability to interact with NIH3T3 endogenous Axl receptor since it can be abolished by soluble Axl extracellular domain and activates both Axl intrinsic kinase activity and the downstream MAPK pathway. Moreover when ectopic Axl overexpression is performed by microinjection in serum starved NIH3T3 cells, addition of a non mitogenic level of Gas6 induces selective entry into S phase in Axl overexpressing cells. Interestingly, Axl overexpression per se is not able to induce S phase entry. Finally we present evidences indicating that Gas6 is able to protect serum starved NIH3T3 cells from cell death by apoptosis as induced by complete growth factor depletion. The reported survival activity seems to be independent of Gas6 mitogenic activity, thus implicating a double and separable activity for Gas6 during growth arrest.

3T3 Cells↗
PubMed2006

Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival.

Malignant gliomas remain incurable brain tumors because of their diffuse-invasive growth. So far, the genetic and molecular events underlying gliomagenesis are poorly understood. In this study, we have identified the receptor tyrosine kinase Axl as a mediator of glioma growth and invasion. We demonstrate that Axl and its ligand Gas6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions. Furthermore, Axl is expressed at high levels in human malignant glioma. Inhibition of Axl signaling by overexpression of a dominant-negative receptor mutant (AXL-DN) suppressed experimental gliomagenesis (growth inhibition >85%, P < 0.05) and resulted in long-term survival of mice after intracerebral glioma cell implantation when compared with Axl wild-type (AXL-WT) transfected tumor cells (survival times: AXL-WT, 10 days; AXL-DN, >72 days). A detailed analysis of the distinct hallmarks of glioma pathology, such as cell proliferation, migration, and invasion and tumor angiogenesis, revealed that inhibition of Axl signaling interfered with cell proliferation (inhibition 30% versus AXL-WT), glioma cell migration (inhibition 90% versus mock and AXL-WT, P < 0.05), and invasion (inhibition 62% and 79% versus mock and AXL-WT, respectively; P < 0.05). This study describes the identification, functional manipulation, in vitro and in vivo validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. Our findings implicate Axl in gliomagenesis and validate it as a promising target for the development of approaches toward a therapy of these highly aggressive but, as yet, therapy-refractory, tumors.

Animals↗
PubMed1997

The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation.

The product of gas6 (Gas6) is a growth factor with high level of similarity to protein S and was identified as the ligand for Axl family of tyrosine kinase receptors. Gas6 contains an N-terminal gamma-carboxylated domain (Gla), four epidermal growth factor like domains and a large C-terminal D region. An alternative Gas6 spliced form (Gas6SV) having an additional 43 amino acids between fourth EFG like and D domain was characterised. Here we show data indicating that Gas6SV is specifically cleaved within the inserted sequence, thereby splitting the D domain from the remaining part of the protein. The resulting two proteolytic products of 36 kDa and 50 kDa were separated and the 50 kDa fragment corresponding to region D was shown to be responsible for Axl receptor activation. Furthermore a deletion mutant of Gas6 containing only the D domain was shown to similarly activate Axl receptor phosphorylation unequivocally demonstrating that D domain can act as a signalling molecule. The possible roles of the proteolytic processing of Gas6SV in the regulation of growth factor availability are discussed.

Alternative Splicing↗
PubMed1994

Activation of the Axl receptor tyrosine kinase induces mitogenesis and transformation in 32D cells.

axl is a transforming receptor tyrosine kinase isolated from DNA of patients with chronic myelogenous leukemia. Association of axl expression with myelogenous leukemias and its expression in primitive hematopoietic cells suggests a role for axl in myeloid biology. To study the cellular function of axl, we constructed a chimeric receptor tyrosine kinase composed of the extracellular and transmembrane domains of the EGF receptor and the cytoplasmic domain of axl; this chimera was named EAK for EGFR-Axl-Kinase. The EAK chimeric receptor was expressed in the mouse myeloid progenitor cell line 32D, which is dependent on interleukin 3 (IL-3) for proliferation and survival. Treatment of the 32D-EAK cells with EGF stimulated the tyrosine phosphorylation of the axl kinase domain and enabled proliferation through EGF rather than IL-3. Thus, axl can effectively couple with mitogenic signaling pathways intrinsic to 32D myeloid cells. Assay of proteins phosphorylated in response to different cytokine treatments showed that IL-3 and EGF exposure produced unique profiles in the 32D-EAK cells. Furthermore, Jak-2 is phosphorylated only in response to IL-3 treatment in these cells. This suggests that IL-3 receptor and axl transduce mitogenic signals through separate pathways. In addition, exposure of cells expressing the chimeric receptor to EGF for 19 days converted the cells to factor-independent growth, a phenomenon not seen with other receptor tyrosine kinases. Generation of this transformed phenotype is absolutely dependent on axl activation by foster ligand. The tyrosine phosphorylation level of the axl kinase domain in the factor-independent subclones is 40-fold greater than the factor-dependent cells. The association of a unique axl phosphorylation level with the factor-independent phenotype suggests that there is a threshold phosphorylation level of the axl kinase for transformation. The fact that activation of the axl receptor leads to transformation of 32D cells suggests that axl can play a role in leukemic conversion of myeloid cells, either through inappropriate expression or improper activation.

Animals↗
PubMed2003

Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes.

Vascular pericytes undergo osteogenic differentiation in vivo and in vitro and may, therefore, be involved in diseases involving ectopic calcification and osteogenesis. The purpose of this study was to identify factors that inhibit the entry of pericytes into this differentiation pathway. RNA was prepared from pericytes at confluence and after their osteogenic differentiation (mineralized nodules). Subtractive hybridization was conducted on polyA PCR-amplified RNA to isolate genes expressed by confluent pericytes that were downregulated in the mineralized nodules. The subtraction product was used to screen a pericyte cDNA library and one of the positive genes identified was Axl, the receptor tyrosine kinase. Northern and Western blotting confirmed that Axl was expressed by confluent cells and was downregulated in mineralized nodules. Western blot analysis demonstrated that confluent pericytes also secrete the Axl ligand, Gas6. Immunoprecipitation of confluent cell lysates with an anti-phosphotyrosine antibody followed by Western blotting using an anti-Axl antibody, demonstrated that Axl was active in confluent pericytes and that its activity could not be further enhanced by incubating the cells with recombinant Gas6. The addition of recombinant Axl-extracellular domain (ECD) to pericyte cultures inhibited the phosphorylation of Axl by endogenous Gas6 and enhanced the rate of nodule mineralization. These effects were inhibited by coincubation of pericytes with Axl-ECD and recombinant Gas6. Together these results demonstrate that activation of Axl inhibits the osteogenic differentiation of vascular pericytes.

Animals↗
PubMed1996

Differential activation of the Ras/extracellular-signal-regulated protein kinase pathway is responsible for the biological consequences induced by the Axl receptor tyrosine kinase.

To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF receptor-Axl kinase]). We have previously shown that upon exogenous EGF stimulation, 32D-EAK cells are capable of proliferation in the absence of interleukin-3. With this system, we determined that EAK-induced cell survival and mitogenesis are dependent upon the Ras/extracellular-signal-regulated protein kinase (ERK) cascade. Although the phosphatidylinositol-3 kinase pathway is activated upon EAK signaling, it appears to be dispensable for the biological actions of the Axl kinase. Furthermore, we demonstrated that different threshold levels of Ras/ERK activation are needed to induce a block to apoptosis or proliferation in 32D cells. Recently, we have identified an Axl ligand, GAS6. Surprisingly, GAS6-stimulated 32D-Axl cells exhibited no blockage to apoptosis or mitogenic response which is correlated with the absence of Ras/ERK activation. Taken together, these data suggest that different extracellular domains dramatically alter the intracellular response of the Axl kinase. Furthermore, our data suggest that the GAS6-Axl interaction does not induce mitogenesis and that its exact role remains to be determined.

Adaptor Proteins, Signal Transducing↗
PubMed1995

The transforming receptor tyrosine kinase, Axl, is post-translationally regulated by proteolytic cleavage.

Several receptor tyrosine kinases generate soluble ligand binding domains either by differential splicing resulting in a truncated RNA transcript, or by proteolytic cleavage. Although the exact role in vivo of these soluble extracellular domains is unclear, proteolysis may function to down-regulate the receptor, and soluble extracellular domains (ECD) may compete with the intact receptor binding to ligand. Axl is a member of a new class of receptor tyrosine kinases characterized by an ECD resembling cell adhesion molecules and unique sequences in the kinase domain. In addition, Axl is transforming in both fibroblast and hematopoietic cells, and appears to be involved in mesenchymal development. We now find that Axl is post-translationally processed by cleavage in a 14 amino acid region immediately NH2-terminal to the transmembrane domain resulting in a soluble ECD and a membrane bound kinase domain. The sequence of this putative cleavage site shares no homology with recognition sites of known proteases. Characterization of this proteolytic processing shows that it does not require protein synthesis or transport but is augmented by phorbol ester treatment. Since the cleavage of Axl enhances turnover of the kinase on the cell surface, we suggest that proteolytic processing down-regulates Axl kinase activity.

3T3 Cells↗
PubMed2005

The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases.

Axl belongs to a particular subfamily of transmembrane receptor tyrosine kinases, the biological ligand for which is the growth/survival factor Gas6. However, little is known about the molecular mechanisms for Axl activation and signal transduction. We have previously identified a novel interaction between the intracellular domain of Axl and Ran binding protein in microtubule organising centre (RanBPM). In the present study, we investigated further the nature of the RanBPM interaction with Axl. A wide distribution of RanBPM mRNA expression in human tissues and various human cancer cell lines was detected. The strength of interaction of both proteins in yeast was comparable to that with the other Axl-binding proteins phosphatidylinositol 3-kinase and Grb2. A truncated version of RanBPM with the SPRY-LisH domain region omitted failed to interact with Axl in yeast. RanBPM was also found to interact in yeast with the Axl homologue, Sky/Tyro3. The interaction between Axl intracellular domain and RanBPM was reproduced in coimmunoprecipitation experiments in both cell-free and mammalian cell systems. Furthermore, coimmunoprecipitation revealed endogenous Axl and RanBPM to interact in several mammalian cell lines in a constitutive manner. Stimulation of COS cells with Gas6 caused increased Axl tyrosine phosphorylation although appeared not to influence the RanBPM-Axl association. In conclusion, we have identified and characterised a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. This novel insight into the signalling interactions of Axl and Sky may shed further light on their suspected roles in tumourigenesis, inflammation as well as other cell proliferative diseases.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis.

We demonstrated the expression of Gas6, the protein product of the growth arrest-specific gene 6 (gas6) and a member of the vitamin K-dependent protein family, and its receptor tyrosine kinases, Axl and Sky, in human uterine and ovarian endometriotic endometria using RT-PCR-Southern blot analysis and immunohistochemistry. Gas6, Axl and Sky mRNA were detected in all samples analysed. There was no significant difference between the levels of Sky mRNA in normal uterine and endometriotic endometria; however, the levels of Gas6 and Axl mRNA in endometriotic endometria were significantly higher than in normal endometria. These mRNA levels showed no significant alteration during the menstrual cycle. In the immunohistochemical study, Gas6, Axl and Sky were found in endometrial glandular cells and stromal cells in all samples analysed. This study demonstrates the coexpression of receptor tyrosine kinases and their ligand, Gas6, in normal uterine and ovarian endometriotic endometria, and the overexpression of Axl and Gas6 in endometriotic endometria. It is suggested that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential.

Adult↗
PubMed2006

Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours.

The molecular mechanisms that underlie the development of squamous cell skin cancers (SSC) are poorly understood. We have used oligonucleotide microarrays to compare the differences in cellular gene expression between a series of keratinocyte cell that mimic disease progression with the aim of identifying genes that may potentially contribute towards squamous cell carcinoma (SCC) progression in vivo, and in particular to identify markers that may serve as potential therapeutic targets for SCC treatment. Gene expression differences were corroborated by polymerase chain reaction and Western blotting. We identified Axl, a receptor tyrosine kinase with transforming potential that has also been shown to have a role in cell survival, adhesion and chemotaxis, was upregulated in vitro in SCC-derived cells compared to premalignant cells. Extending the investigation to tumour biopsies showed that the Axl protein was overexpressed in vivo in a series of SCCs.

Biomarkers, Tumor↗
PubMed2001

Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast.

BACKGROUND: Axl, a member of a family of receptor tyrosine kinases characterized by an extracellular domain resembling cell adhesion molecules and an intracellular conserved tyrosine kinase domain has been reported to induce cell proliferation and transformation. In mice, axl is expressed in the normal mammary gland and over-expressed in aggressive mammary tumors. PATIENTS AND METHODS: We have investigated the expression of axl immunohistochemically in 23 normal human breast samples and in 111 consecutive breast carcinomas. Expression of axl was correlated with tumour characteristics (lymph node involvement, stage, grade) and immunohistochemical expression of ER, PR, Ki-67 and c-erbB-2. RESULTS: In normal tissue, axl localizes to the membrane of breast epithelial cells. Axl protein shows membrane associated staining in high correlation (P = 0.004) with the expression of the estrogen receptor (ER). Axl expression was found in a subset of breast carcinomas and was also correlated with high significance (P < 0.0001) with the presence of ER. CONCLUSION: Our results suggest that axl may serve as a mediator of estrogen stimulation preventing the completion of the breast epithelial life cycle and that estrogen induced axl expression may give a survival signal to cancerous cells, preventing them from dying through apoptosis.

Adolescent↗
PubMed2002

Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin.

Axl receptor tyrosine kinase is implicated in several malignancies and is the receptor for the vitamin K-dependent growth factor Gas6. From a yeast two-hybrid screen of protein-protein interactions with the Axl cytoplasmic domain, we detected a previously uncharacterised SH2 domain-containing protein. We cloned two novel splice variants of this protein that give rise to 1409- and 1419-amino acid proteins, differing only in their N-terminal residues and yielding a 150-kDa protein product by in vitro translation. The Axl-interacting C-terminus contains a tandem SH2 and PTB domain combination homologous to the focal adhesion protein tensin. We detected interaction of Axl with both domains in mammalian cells by co-immunoprecipitation and two-hybrid analyses. In addition, the protein possesses an N-terminal putative phorbol ester-binding C1 domain as well as a central tyrosine phosphatase motif. Thus, we have named the protein C1 domain-containing phosphatase and TENsin homologue (C1-TEN). Northern blot analysis of C1-TEN in human tissues revealed highest expression in heart, kidney, and liver. In summary, we have identified a novel multi-domain intracellular protein that interacts with Axl and which may furthermore be involved in other signal transduction pathways.

Alternative Splicing↗
PubMed1995

Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6.

The Axl receptor tyrosine kinase was identified as a protein encoded by a transforming gene from primary human myeloid leukaemia cells by DNA-mediated transformation of NIH 3T3 cells. Axl is the founding member of a family of related receptors that includes Eyk, encoded by a chicken proto-oncogene originally described as a retroviral transforming gene, and c-Mer, encoded by a human proto-oncogene expressed in neoplastic B- and T-cell lines. The transforming activity of Axl demonstrates that the receptor can drive cellular proliferation. The function of Axl in non-transformed cells and tissues is unknown, but may involve the stimulation of cell proliferation in response to an appropriate signal, namely a ligand that activates the receptor. We report here the purification of an Axl stimulatory factor, and its identification as the product of growth-arrest-specific gene 6 (ref. 6). This is, to our knowledge, the first description of a ligand for the Axl family of receptors.

Amino Acid Sequence↗