Abl tyrosine kinase
Bcr/Abl oncoproteins were tested for interactions with
cytoplasmic proteins that mediate Ras activation. Such polypeptides include Grb2, which comprises a single Src homology 2 (SH2)
domain flanked by two SH3 domains, and the 66, 52 and 46 kDa Shc proteins, which all possess an SH2 domain in their
carboxy-terminus. Grb2 associates with tyrosine phosphorylated proteins through its SH2 domain, and with the Ras guanine
nucleotide releasing protein mSos1 through its SH3 domains. mSos1 stimulates conversion of the inactive GDP-bound form of Ras to
the active GTP-bound state. In bcr-abl-transformed cells, Grb2 and mSos1 form a physical complex with Bcr/Abl. In vitro, the
Grb2 SH2 domain binds Bcr/Abl through recognition of a tyrosine phosphorylation site within the amino-terminal bcr-encoded
sequence (p.Tyr177-Val-Asn-Val) common to both Bcr/Abl proteins. These results suggest that autophosphorylation within the
Bcr element of Bcr/Abl creates a direct physical link to Grb2-mSos1, and potentially to the Ras pathway, and thereby modifies the
target specificity of the Abl tyrosine kinase (Puil, 1994).
A 62 kDa protein is highly phosphorylated in many cells containing activated tyrosine
kinases. This protein, characterized mainly by its avid association with rasGAP, has
proved difficult to identify. In this study, anti-phosphotyrosine antibody was used to purify p62. Based on its peptide
sequence, molecular cloning reveals a cDNA encoding a novel protein, p62dok, with
little homology to other proteins but with a prominent set of tyrosines and nearby sequences
suggestive of SH2 binding sites. v-Abl tyrosine kinase binds and strongly
phosphorylates p62dok, which then binds rasGAP. 2C4A, a monoclonal antibody to the
rasGAP-associated p62, reacts with p62dok. Thus, p62dok appears to be the
long-sought major substrate of many tyrosine kinases (Yamanashi, 1997).
Ras is a necessary downstream element of Abelson murine leukemia virus
(Ab-MLV)-mediated transformation. It can be activated by the
phosphotyrosine-dependent association of Shc with the Grb2-mSos complex. Shc is tyrosine-phosphorylated and associates with Grb2 in
v-Abl-transformed cells, whereas Shc in NIH3T3 cells is phosphorylated solely on
serine and is not Grb2-associated. Shc coprecipitates with P120 v-Abl and with
P70 v-Abl (which lacks the carboxyl terminus). Surprisingly, a kinase-defective mutant
of P120 also binds Shc, demonstrating that Shc/v-Abl association is a
phosphotyrosine-independent interaction. Shc from both NIH3T3
and v-Abl-transformed cells binds to the Abl SH2 domain; P120 v-Abl binds
to a region in the amino terminus of Shc. Consistent with these data, a v-Abl mutant
encoding only the Gag and SH2 regions is able to bind Shc in vivo. The unique
non-phosphotyrosine-mediated binding of Shc may allow direct tyrosine
phosphorylation of Shc by v-Abl and subsequent activation of the Ras pathway
through assembly of a signaling complex with Grb2-mSos (Raffel, 1996).
BCR/ABL is a chimaeric oncogene generated by translocation of sequences from the c-ABL
protein-tyrosine kinase gene on chromosome 9 into the BCR (breakpoint cluster region) gene on chromosome 22. Alternative
chimeric proteins, p210(BCR/ABL) and p190(BCR/ABL), are produced that are characteristic of
chronic myelogenous leukemia and acute lymphoblastic leukemia, respectively. Their role in the
etiology of human leukemia remains to be defined. The tumorigenic
effect of BCR/ABL oncogenes is mediated by Bcl-2. Bcl-2 is a protein essential for
transformation by BCR/ABL. However, it is not known how Bcl-2 and Ras fit together in cell
transformation by BCR/ABL. The data presented here establish that Bcl-2 is a downstream target
gene of the Ras signaling pathway in cells transformed by BCR/ABL, and that constitutive Ras
activation results in constitutive expression of the gene. Conversely, a truncated form of the
BCR/ABL, which lacks a critical BCR region required for activation of the Ras signaling pathway,
fails to induce Bcl-2 expression. These results indicate that BCR/ABL prevents apoptosis by inducing
Bcl-2 through a signaling pathway involving Ras and links constitutive Ras activation and Bcl-2 gene
regulation. Hence, these results further imply that Ras is involved in both mitogenic signals and survival
signals (Sanchez-Garcia, 1997).
v-Abl induces
transcription of c-myc, and c-Myc function is a necessary but not sufficient
component of the v-Abl transformation program. The E2F
site in the c-myc promoter is a v-Abl response element. v-Abl appears to
induce c-myc by initiating a phosphorylation cascade that ultimately activates
E2F-binding proteins. The Ras
GTPase and Raf1 serine/threonine kinase are required in this pathway. However, in
contrast to other aspects of v-Abl signaling, induction of c-myc transcription is
independent of the Rac GTPase. These results also establish a requirement for activated
cyclin-dependent kinases (cdks), as v-Abl-dependent induction of c-myc transcription
is blocked by cdk inhibitor p21 and induction of c-myc is accompanied by activation of
cdk2 and cdk4. v-Abl-dependent induction of c-myc is
accompanied by hyperphosphorylation of pRb, p107, and p130 (Zou, 1997).
Drosophila disabled interacts genetically with Abl oncogene, Disabled-2 (Dab2), a mammalian structural homolog of Drosophila Disabled is a mitogen-responsive phosphoprotein. It has been speculated to be a negative regulator of growth since its expression is lost in ovarian carcinomas. Dab2 contains a C-terminal proline-rich domain with sequences similar to those found in Sos, a guanine nucleotide exchange factor for Ras (see Drosophila Ras). The proline-rich
sequences of Sos mediate the interaction of Sos with Grb2, an adaptor protein which coupled tyrosine
kinase receptors to Sos. The possibility that Dab2 interacts with Grb2 has been investigated. In
experiments of co-immunoprecipitation from BAC1.2F5 macrophage cell lysates, significant quantities
of Grb2 are associated with both Sos and Dab2, although Dab2 and Sos were not present in the same
complex. Transfection of Dab2 into a Dab2-negative cell line (293 cells) decreases the amount of Grb2
associated with Sos, suggesting that Dab2 competes with Sos for binding to Grb2. Proline-rich peptides
corresponding to Dab2 (#661-669) and to Sos (#1146-1161) inhibit the binding of Dab2 to Grb2, but
are less effective in disrupting the Grb2-Sos complex. The expressed proline-rich domain of Dab2
(#600-730) binds Grb2, but other regions of Dab2 fail to bind Grb2. Both of the individual SH3
domains of Grb2 bind to Sos (the N-terminal SH3 domain of Grb2 has a greated affinity than C-terminal SH3 domain), but binding to
Dab2 requires the intact Grb2, suggesting cooperative binding using both SH3 domains of Grb2. These
data indicate that Dab2 binds to the SH3 domains of Grb2 via its C-terminal proline-rich sequences.
Dab2 may modulate growth factor/Ras pathways by competing with Sos for binding to Grb2. While the N-terminal region of Dab2 and Drosophila Dab show significant homology to one another (both contain the PID domain), the C-terminal proline-rich domain of Dab2 differes significantly from that of Drosophila Dab. However, the C-terminal half of Drosophila Dab also contains several stretches of proline-rich sequences, which might function analgously to those in Dab2. Thus, it is possible that Drosophila Dab binds to a homologous SH2-containing Drosophila proteins, such as the Grb2 homolog Drk2 (Xu, 1998).
The phenotype of hematopoietic cells transformed by the BCR/ABL oncoprotein of the Philadelphia chromosome is
characterized by growth factor-independent proliferation, reduced susceptibility to apoptosis, and altered adhesion and
motility. The mechanisms underlying this phenotype are not fully understood, but there is evidence that some of the
properties of BCR/ABL-expressing cells are dependent on the activation of downstream effector molecules such as RAS,
PI-3k, and bcl-2. It is shown that the small GTP-binding protein Rac is activated by BCR/ABL in a tyrosine
kinase-dependent manner. Upon transfection with a vector carrying the dominant-negative N17Rac, BCR/ABL-expressing
myeloid precursor 32Dcl3 cells retain the resistance to growth factor deprivation-induced apoptosis but show a
decrease in proliferative potential in the absence of interleukin-3 (IL-3) and markedly reduced invasive properties.
Moreover, compared with BCR/ABL-expressing cells, fewer BCR/ABL plus N17Rac double transfectants are capable of
homing to bone marrow and spleen. Consistent with these findings, survival of SCID mice injected with the BCR/ABL
plus N17Rac double transfectants is markedly prolonged, when compared with that of mice injected with
BCR/ABL-expressing cells. Together, these data support the important role of a Rac-dependent pathway(s) controlling
motility in BCR/ABL-mediated leukemogenesis (Skorski, 1998).
The non-receptor tyrosine kinase Abl participates in receptor tyrosine kinase (RTK)-induced actin cytoskeleton remodelling, a signalling pathway in which the function of Rac is pivotal. More importantly, the activity of Rac is indispensable for the leukaemogenic ability of the BCR-Abl oncoprotein. Thus, Rac might function downstream of Abl and be activated by it. This study elucidates the molecular mechanisms through which Abl signals to Rac in RTK-activated pathways. Sos-1, a dual guanine nucleotide-exchange factor (GEF), is phosphorylated on tyrosine, after activation of RTKs, in an Abl-dependent manner. Sos-1 and Abl interact in vivo, and Abl-induced tyrosine phosphorylation of Sos-1 is sufficient to elicit its Rac-GEF activity in vitro. Genetic or pharmacological interference with Abl (and the related kinase Arg) results in a marked decrease in Rac activation induced by physiological doses of growth factors. Thus, these data identify the molecular connections of a pathway RTKs-Abl-Sos-1-Rac that is involved in signal transduction and actin remodelling (Sini, 2004).
The development of neuronal polarity is essential for the determination of neuron connectivity and for correct brain function. The c-Jun N-terminal kinase (JNK)-interacting protein-1 (JIP1) is highly expressed in neurons and has previously been characterized as a regulator of JNK signaling. JIP1 has been shown to localize to neurites in various neuronal models, but the functional significance of this localization is not fully understood. JIP1 is also a cargo of the motor protein kinesin-1, which is important for axonal transport. This study demonstrated that before primary cortical neurons become polarized, JIP1 specifically localizes to a single neurite and that after axonal specification, it accumulates in the emerging axon. JIP1 is necessary for normal axonal development and promotes axonal growth dependent upon its binding to kinesin-1 and via a newly described interaction with the c-Abl tyrosine kinase. JIP1 associates with and is phosphorylated by c-Abl, and the mutation of the c-Abl phosphorylation site on JIP1 abrogates its ability to promote axonal growth. The kinesin-1-dependent localization of JIP1 to developing axonal growth cones and its colocalization with dynamic microtubules and exploratory processes emanating from the growth cone suggest that it may be important for the regulation of cytoskeletal structures. c-Abl is a well-established regulator of cytoskeletal dynamics, and JIP1 may be an important downstream effector of c-Abl in cytoskeletal reorganization. The JIP1 scaffold protein, therefore, has the potential to act as a crucial link between extracellular signals and the regulation of cytoskeletal dynamics that lead to axonal development (Dajas-Bailador, 2008).
The tyrosine kinase c-Abl (see Drosophila Abl) participates in the regulation of various cellular functions including cell proliferation, adhesion, migration, smooth muscle contraction and cancer progression. However, knowledge regarding transcriptional regulation of c-Abl is surprisingly limited. Sp1 is a founding member of the Sp1 transcription factor family that has been implicated in housekeeping gene expression, tumor cell proliferation and differentiation. This study shows that knockdown and rescue of Sp1 affected growth factor-mediated c-Abl expression in cells. c-Abl promoter activity was also affected by Sp1 knockdown. This is the first evidence to suggest that Sp1 is an important transcription factor to regulate c-Abl expression. In addition, Sp1 phosphorylation at Thr-453 and Thr-739 has been proposed to regulate its activity in Drosophila cells. It was unexpectedly found that growth factors did not induce Sp1 phosphorylation at these two residues. In contrast, growth factor stimulation upregulated Sp1 expression. Intriguingly, inhibition of ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) reduced expression of Sp1 and c-Abl. Furthermore, c-Abl knockdown diminished ERK1/2 phosphorylation and Sp1 expression. Taken together, these studies suggest that Sp1 can modulate c-Abl expression at transcription level. Conversely, c-Abl affects ERK1/2 activation and Sp1 expression in cells (Long, 2019).
The c-Abl tyrosine kinase localizes to the cytoplasm and plasma membrane in addition to the nucleus. However, there is little
information regarding a role for c-Abl in the cytoplasm/plasma membrane compartments. A membrane pool of c-Abl is activated by the growth factors PDGF and EGF in fibroblasts. The pattern and kinetics of activation are similar to growth
factor activation of Src family kinases. To determine whether a link exists between activation of c-Abl and members of the Src family, c-Abl kinase activity was examined in cells that express oncogenic Src proteins. c-Abl kinase activity is increased by 10- to 20-fold in these cells, and Src and Fyn kinases are shown to directly phosphorylate c-Abl in vitro. Furthermore, overexpression of wild-type Src potentiates c-Abl activation by growth factors, and a kinase-inactive form of Src reduces this activation, showing that Abl activation by growth factors occurs at least in part via activation of Src kinases. Significantly, c-Abl has a functional
role in the morphological response to PDGF. Whereas PDGF treatment of serum-starved wild-type mouse embryo fibroblasts results in distinct linear or circular/dorsal membrane ruffling, c-Abl-null cells demonstrate dramatically reduced ruffling in response to PDGF, which is rescued by physiological re-expression of c-Abl. These data identify c-Abl as a downstream target of activated receptor tyrosine kinases and Src family kinases, and show for the first time that c-Abl functions in the cellular response to growth factors (Plattner, 1999).
Tight regulation of cell motility is essential for many physiological processes, such as formation of a functional nervous system and wound healing. Drosophila Abl negatively regulates the actin cytoskeleton effector protein Ena during neuronal development in flies, and it has been postulated that this may occur through an unknown intermediary. Lamellipodin (Lpd) regulates cell motility and recruits Ena/VASP proteins (Ena, Mena, VASP, EVL) to the leading edge of cells. However, the regulation of this recruitment has remained unsolved. This study shows that Lpd is a substrate of Abl kinases and binds to the Abl SH2 domain. Phosphorylation of Lpd positively regulates the interaction between Lpd and Ena/VASP proteins. Consistently, efficient recruitment of Mena and EVL to Lpd at the leading edge requires Abl kinases. Furthermore, transient Lpd phosphorylation by Abl kinases upon netrin-1 stimulation of primary cortical neurons positively correlates with an increase in Lpd-Mena coprecipitation. Lpd is also transiently phosphorylated by Abl kinases upon platelet-derived growth factor (PDGF) stimulation, regulates PDGF-induced dorsal ruffling of fibroblasts and axonal morphogenesis, and cooperates with c-Abl in an Ena/VASP-dependent manner. These findings suggest that Abl kinases positively regulate Lpd-Ena/VASP interaction, Ena/VASP recruitment to Lpd at the leading edge, and Lpd-Ena/VASP function in axonal morphogenesis and in PDGF-induced dorsal ruffling. These data do not support the suggested negative regulatory role of Abl for Ena. Instead, it is proposed that Lpd is the hitherto unknown intermediary between Abl and Ena/VASP proteins (Michael, 2010).
Drosophila ena was originally identified as a suppressor of lethality induced by mutations in Drosophlia abl, and it was postulated that abl and ena negatively regulate each other. Both the Abl tyrosine kinase family (Drosophila Abl, vertebrate c-Abl and Arg) and the Ena/VASP family (Ena, vertebrate Mena, VASP, and EVL) act downstream of the netrin-1 axon guidance receptor DCC and regulate cell motility. Abl kinases regulate platelet-derived growth factor (PDGF)-induced dorsal ruffling of fibroblasts, but it is not known whether Lamellipodin (Lpd) or Ena/VASP proteins function in this pathway (Michael, 2010).
Ena/VASP proteins play a crucial role in cell motility by antagonizing actin filament capping. This alters the geometry of the actin network toward longer, less-branched filaments, thereby changing the speed and persistence of lamellipodia. Ena/VASP proteins are recruited to the leading edge through interactions between their EVH1 domain and FP4 motifs within Lpd, a member of the MRL family of Ras effector proteins, which includes C. elegans MIG-10, vertebrate RIAM and Lpd, and Drosophila Pico (Lyulcheva, 2008). Lpd contains a proline-rich region harboring potential SH3-binding sites and a PH domain that mediates membrane targeting. It has been shown that Lpd is required for lamellipodia formation and that Lpd overexpression increases the speed of lamellipodial protrusion in an Ena/VASP-dependent manner (Michael, 2010).
Lpd-dependent recruitment of Ena/VASP proteins to the leading edge needs to be tightly regulated in order to precisely control lamellipodia formation, but it is not known how this is achieved. Studies in Drosophila have suggested that Abl regulates Ena localization. Yet how the localization of Ena/VASP proteins is controlled, and whether Abl plays a role in this process in vertebrates, remains unclear (Michael, 2010).
This study shows that phosphorylation of Lpd by c-Abl increases its interaction with Ena/VASP proteins. Consistently, efficient recruitment of Mena and EVL to Lpd-positive lamellipodia requires Abl kinases. Evidence is provided that Lpd and Ena/VASP proteins regulate dorsal ruffling of fibroblasts upon PDGF treatment and that Lpd function in this process is controlled by Abl kinases and mediated by Ena/VASP proteins. Furthermore, it was demonstrated that both Lpd and c-Abl cooperate during axonal morphogenesis in an Ena/VASP-dependent manner. The data do not support the suggested antagonistic roles of Abl and Ena, and an alternative hypothesis is proposed that Abl kinases, via Lpd, positively regulate Ena/VASP proteins (Michael, 2010).
The c-Abl and Arg proteins comprise a unique family of nonreceptor
tyrosine kinases that have been implicated in the regulation of cell
proliferation and survival, cytoskeletal reorganization, cell
migration, and the response to oxidative stress and DNA damage.
Targeted deletion or mutation of c-Abl in mice results in a variety
of immune system phenotypes, including splenic and thymic atrophy,
lymphopenia, and an increased susceptibility to infection. However,
despite the generation of these mice over a decade ago, little is
known regarding the mechanisms responsible for these phenotypes or
the immune-related consequences of ablation of both the c-Abl and Arg
kinases, which are coexpressed in lymphoid tissues. T cell receptor
(TCR) stimulation is shown to result in activation of the endogenous
Abl kinases. Zap70 and the transmembrane adaptor linker for
activation of T cells (LAT) are targets of the Abl kinases, and loss
of Abl kinase activity reduces TCR-induced Zap70 phosphorylation at
tyrosine 319. This correlates with diminished LAT tyrosine
phosphorylation, as well as reduced tyrosine phosphorylation and
recruitment of phospholipase Cγ1 to LAT. Significantly, Abl
kinase activity is required for maximal signaling leading to
transcription of the IL-2 promoter, as well as TCR-induced IL-2
production and proliferation of primary T cells. It is concluded that
the Abl kinases have a role in the regulation of TCR-mediated signal
transduction leading to IL-2 production and cell proliferation
(Zipfel, 2004).
Fertilization causes tyrosine phosphorylation of several sea urchin egg proteins within minutes of sperm-egg binding, although the identity
of the kinase(s) involved and the mechanism of regulation is not known. Antibodies against a homolog of the ABL
family of protein tyrosine kinases expressed in the sea urchin egg identify a 220-kDa protein kinase, highly enriched in the egg cortex, where it is
tightly associated with detergent-insoluble cytoskeletal elements. The enzyme is capable of phosphorylating synthetic peptide
substrates that were used to characterize the kinase activity in an immune-complex assay. Measurement of the protein tyrosine
kinase activity immunoprecipitates at different times after fertilization, revealing that the level of kinase activity is transiently elevated
during the first few minutes postinsemination. The amount of the 220-kDa protein does not increase
significantly during this period, so the increased kinase activity probably results from activation of the enzyme. These in vitro studies
indicate that the 220-kDa Abl-related kinase is one of the protein kinases activated during fertilization and suggest that it may play a role
in the egg activation process (Moore, 1994).
The Abl and Arg (the Abl-related
gene) tyrosine kinases play fundamental roles in the development and function of the central nervous system.
Arg is most abundant in adult mouse brain, especially in synapse-rich regions. arg(-/-) mice develop normally but exhibit
multiple behavioral abnormalities, suggesting that arg(-/-) brains suffer from defects in neuronal function. Embryos
deficient in both Abl and Arg suffer from defects in neurulation and die before 11 days postcoitum. Although they
divide normally, abl(-/-);arg(-/-) double mutant neuroepithelial cells display gross alterations in their actin cytoskeleton. Abl
and Arg colocalize with one another and with actin microfilaments at the apical surface of the developing neuroepithelium.
Thus, Abl and Arg play essential roles in neurulation and can regulate the structure of the actin cytoskeleton (Koleske, 1998).
Cell adhesion regulates the
kinase activity and subcellular localization of c-Abl. When fibroblastic cells are
detached from the extracellular matrix, kinase activity of both cytoplasmic and nuclear
c-Abl decreases, but there is no detectable alteration in the subcellular distribution.
Upon adhesion to the extracellular matrix protein fibronectin, a transient recruitment of
a subset of c-Abl to early focal contacts is observed coincident with the export of
c-Abl from the nucleus to the cytoplasm. The cytoplasmic pool of c-Abl is reactivated
within 5 min of adhesion, but the nuclear c-Abl is reactivated after 30 min, correlating
closely with its return to the nucleus and suggesting that the active nuclear c-Abl
originates in the cytoplasm. In quiescent cells where nuclear c-Abl activity is low, the
cytoplasmic c-Abl is similarly regulated by adhesion but the nuclear c-Abl is not
activated upon cell attachment. These results show that c-Abl activation requires cell
adhesion and that this tyrosine kinase can transmit integrin signals to the nucleus
where it may function to integrate adhesion and cell cycle signals (Lewis, 1996).
Abl interactions with the cytoskeleton
The myristoylated form of c-Abl protein, as well as the P210bcr/abl protein, have been shown to
associate with F-actin stress fibers in fibroblasts. The
domain responsible for this interaction maps to the extreme COOH-terminus of Abl. The actin-binding domain is localized to a 58 amino acid region, including a charged motif at the
extreme COOH-terminus that is important for efficient binding. F-actin binding by Abl is calcium independent; Abl competes with
gelsolin for binding to F-actin. In addition to the F-actin binding domain, the COOH-terminus of Abl contains a proline-rich region that
mediates binding and sequestration of G-actin. The Abl F- and G-actin binding domains cooperate to bundle F-actin filaments in
vitro. The COOH terminus of Abl thus confers several novel localizing functions upon the protein, including actin binding, nuclear
localization, and DNA binding. Abl may modify and receive signals from the F-actin cytoskeleton in vivo, and is an ideal candidate to
mediate signal transduction from the cell surface and cytoskeleton to the nucleus (Van Etten, 1994).
BCR/ABL, is localized to the actin cytoskeleton. One of the major
tyrosine phosphoproteins in cells transformed by p210BCR/ABL is the proto-oncoprotein p120c-Cbl.
p210BCR/ABL induces formation of a multimeric complex of proteins, including p120c-Cbl, phosphotidylinositol-3' kinase, and
p210BCR/ABL itself. Certain focal adhesion proteins are also part of this complex, including paxillin and talin. The
sites in paxillin required for binding to p120c-Cbl in this complex have been partially mapped. The interaction of pl20c-Cbl with paxillin is
specific, since other focal adhesion proteins, such as p125FAK, vinculin, and alpha-actinin, are not in this complex. The binding of
p120c-Cbl to the focal adhesion protein paxillin could contribute to the known adhesive defects of CML cells (Salgia, 1996).
Proper regulation of cell morphogenesis and migration by adhesion and growth-factor receptors requires Abl-family tyrosine kinases. Several substrates of Abl-family kinase have been identified, but they are unlikely to mediate all of the downstream actions of these kinases on cytoskeletal structure. A human protein microarray was used to identify the actin-regulatory protein cortactin as a novel substrate of the Abl and Abl-related gene (Arg) nonreceptor tyrosine kinases. Cortactin stimulates cell motility, and its upregulation in several cancers correlates with poor prognosis. Even though cortactin can be tyrosine phosphorylated by Src-family kinases in vitro, Abl and Arg are more adept at binding and phosphorylating cortactin. Importantly, platelet-derived growth-factor (PDGF)-induced cortactin phosphorylation on three tyrosine residues requires Abl or Arg. Cortactin triggers F-actin-dependent dorsal waves in fibroblasts after PDGF treatment and thus results in actin reorganization and lamellipodial protrusion. Evidence is provided that Abl/Arg-mediated phosphorylation of cortactin is required for this PDGF-induced dorsal-wave response. The results reveal that Abl-family kinases target cortactin as an effector of cytoskeletal rearrangements in response to PDGF (Boyle, 2007).
forward to Abl tyrosine kinase Evolutionary Homologs part 3/3 ! back to part 1/3 Home page: The Interactive Fly © 1995, 1996 Thomas B. Brody, Ph.D.
The Interactive Fly resides on the
Abl tyrosine kinase:
Biological Overview
| Regulation
| Developmental Biology
| Effects of Mutation
| References
Society for Developmental Biology's Web server.